Ruppel V.V., Ph.D., veterinary dermatologist. Veterinary Clinic of Neurology, Traumatology and Intensive Care, St. Petersburg.

Pemphigus and discoid lupus erythematosus. Diagnosis Therapeutic approaches. Clinical cases from our practice. Pemphigus (pemphigus). General information

In pemphigus, autoimmune reactions are directed against the desmosomes and hemidesmosomes necessary for the connection of keratinocytes with each other and with the basement membrane. The loss of these relationships is called acantholysis.
In practice, the form of exfoliative pemphigus is more common. Cats and dogs are affected, regardless of gender and age.

In dogs of the Akita Inu and Chow Chow breeds, a predisposition to this disease is noted. The causes leading to the development of the disease include idiopathic, as well as those associated with the use of drugs. Lesions spread to the muzzle and ears, on the fingers, on the abdomen near the nipples, and a generalization of the process can be observed when the lesions are spread over the entire surface of the body. Lesion progression begins with erythematous maculae, followed by pustules, epidermal collars, erosions, and yellow-brown crusts. Clinically, skin lesions may be accompanied by distal limb edema, fever, drowsiness, and lymphadenopathy. Differential diagnoses include pyoderma, dermatophytosis, demodicosis, zinc-dependent dermatosis, discoid lupus erythematosus, erythema multiforme, leishmaniasis, sebadenitis.

Establishing diagnosis

According to the authors, the diagnosis of any autoimmune disease is based on a thorough medical history, assessment of clinical manifestations (both primary lesions and the nature of their further spread), laboratory tests, and response to the proposed therapy.
But the most valuable diagnostic procedure for autoimmune diseases is histopathological examination. Although even this study can lead to confusion if the histology specimens were taken incorrectly. The diagnosis of pemphigus involves cytology from an intact pustule where acantholytic keratinocytes surrounded by normal neutrophils and/or eosinophils in the absence of bacteria can be seen. However, the latter (bacteria) in rare cases may still be present. The final diagnosis is established on the basis of histology. The biopsy is taken with the capture of an intact pustule or, in its absence, with the capture of the crust and underlying skin (although this option may not always be informative). With pyoderma, bacterial proteases, and with dermatophytosis - fungi - destroy intercellular glycoproteins (desmoglein), which leads to acantholysis. In this regard, routinely, in addition to cytology, it is also desirable to carry out crops for dermatophytes. Therapy is based on the use of immunosuppressive agents.
However, until the results of histological examination are obtained, it is recommended to carry out antibiotic therapy with the drug of first choice - cephalexin at the recommended doses (22-30 mg / kg × 12 hours), since it is not always possible to clinically distinguish between pyoderma and pemphigus. After receiving a histopathological diagnosis - pemphigus - immunosuppressive therapy with prednisolone is carried out at a daily dose of 2-4 mg / kg. Examinations of such patients in dynamics are carried out every 14 days, until remission is achieved. According to the authors, remission is determined when no new clinical manifestations of the disease are detected during clinical examination. In this case, there are no pustules, any crusts are easily removed, and the epidermis underlying the crusts is pink and without erosion. Dose reductions of prednisolone should not be done rapidly and reductions in prednisolone dosing suggest a 25% reduction in prednisolone dose every 14 days. It is optimal to achieve a maintenance dose for the dog of 0.25 mg/kg or less, given every other day. If it is not possible to achieve such a minimum dosage, then it is suggested that dogs include additional azathioprine in the therapeutic regimen. The starting dose of azathioprine is 1.0 mg/kg daily. After achieving the effect, the intake of azathioprine is reduced every 2-3 months. In this case, it is recommended to reduce not the dose itself, but the frequency of giving the drug: at first - every other day; then - in the dynamics of decline - 1 time in three days.
Azathioprine should never be given to cats as irreversible bone marrow suppression may occur!

Among the possible side effects in dogs, anemia, leukopenia, thrombocytopenia, pancreatitis can form. In this regard, at the initial stage, every 14 days (for 2 months), then every 30 days (for 2 months) and, finally, every 3 months for the entire period of giving azathioprine, clinical and biochemical blood parameters in dogs should be monitored. In general, when it comes to monitoring the general health of patients treated for pemphigus, it should be remembered that every 6 months, all those who are given glucocorticoids require a routine examination. It includes a clinical and biochemical blood test, a clinical urinalysis and a urine culture for bacterial flora.
Features of therapy in cats is that if it is not possible to reduce the dose of prednisolone, then chlorambucil is introduced into the regimen. Dosing regimen, precautions and monitoring for chlorambucil therapy in cats are the same as for azathioprine in dogs. The initial dose of chlorambucil is 0.1-0.2 mg/kg daily.
Dogs not responding to azathioprine may also be treated with chlorambucil. Vitamin E at doses of 400-800 IU 2 times a day and essential fatty acids can be used as adjuvant therapy in dogs, as they have anti-inflammatory and antioxidant properties.
In dogs, a combination of tetracycline and niacinamide may be used because the combination has many anti-inflammatory and immunomodulatory properties. Which, in turn, allows the use of these drugs for the treatment of various immune-mediated skin diseases, such as discoid lupus erythematosus, lupus onychodystrophy, metatarsal fistula of German shepherds, aseptic panniculitis, vasculitis, dermatomyositis and others. Doses for dogs weighing less than 10 kg are 250 mg of each drug every 8 hours. And for dogs weighing more than 10 kg - 500 mg of both drugs every 8 hours. In the presence of a clinical effect, which can occur no earlier than in a few months, the drugs begin to be reduced - first to a double dose, and then to a single daily dose. Side effects are rare and are usually associated with the use of niacinamide. These include vomiting, anorexia, drowsiness, diarrhea, and elevated serum liver enzymes. Tetracycline may lower the seizure threshold in dogs.
In cats, doxycycline at a dose of 5 mg/kg 1-2 times a day can be used as an immunomodulator. After oral administration of doxycycline, cats must then be given at least 5 ml of water, as otherwise there is a high risk of esophageal stricture. In the absence of success from the proposed therapy with prednisolone (high doses are required) or if there is no success from its various combinations with other agents (antioxidants, immunomodulators), it is suggested to try switching to dexamethasone or triamcinolone as recommendations. The initial dose of drugs is 0.05-0.1 mg / kg 2 times a day, and then gradually reduced in the same way as in the case of prednisolone.
High-dose glucocorticoid pulse therapy is suggested as a last choice for intractable cases of exfoliative pemphigus. After such pulse therapy, upon reaching the effect, continue to give prednisolone at the recommended doses with a gradual decrease in the drug, as described above.

There are two protocols for pulse therapy:

PROTOCOL 1: 11 mg/kg of methylprednisolone sodium succinate (per 250 ml of 5% glucose) intravenously once a day for 3-5 days;
PROTOCOL 2: 11 mg/kg prednisone orally once a day for three consecutive days.

Clinical cases of exfoliative pemphigus in our practice

Case 1 On March 7, 2012, 1.5-year-old Labrador Martin was admitted to our clinic. From the anamnesis it followed that this animal is kept at home, in the summer it is in the country, there are no contacts with other animals, the owners did not have any skin problems. Akana food has been used as feeding for the last three weeks, before that, beef, rice, and buckwheat were present in the diet. There were no seasonal manifestations of Martin's skin disease. At the time of admission, the owners noted severe itching, which was localized in the head, limbs, sides, abdomen, and back of the animal. The damage started a few weeks ago. Antibiotics were used as therapy: ceftriaxone - 7 days; ciprofloxacin - 7 days; ceftazidime - 7 days; Convenia was used two days before admission. According to the owners, such a change of antibiotics was carried out by the attending physician due to the absence of any effect from antibiotic therapy.
Examination revealed multiple lesions, including pustules and mostly crusts on the patient's head, back, abdomen, flanks, and extremities (Figures 1-3).

As differential diagnoses, we considered skin infections (demodecosis, dermatophytosis, secondary pyoderma) and pemphigus foliaceus. The scrapings were negative. The cytology of the smear included single bacteria (which did not correspond much to a similar clinical picture in pyoderma), without neutrophilic phagocytosis. The neutrophils we found in this smear were non-degenerative. At the same time, a significant amount of acantholytic keratinocytes was determined.
A biopsy was suggested, sowing on dermatophytes (the owners refused to sow). As a temporary therapy, it was proposed to continue the trial antibiotic therapy, but to arrive at the appointment after the end of the effect of the convection drug (cefovecin - cephalosporin of the 3rd generation) to conduct preliminary crops in order to select an antibacterial drug. The owners agreed only to a biopsy, unfortunately, without accepting our other proposals, and returned to their doctor for further treatment. After some time, the owners of the animal asked for the results of histology, confirming one of our differential diagnoses - pemphigus foliaceus (Figure 1). They refused to discuss treatment regimens. We do not know about the further fate of this patient.

Case 2 On November 28, 2012, a 2-year-old Scottish Longhair cat named Tori was admitted to our clinic. From the anamnesis it followed that the animal lives in an apartment, the owners of the cat from an early age, the animal had no skin problems at the time of purchase. There was contact with a domestic cat 2 months prior to the onset of problems, and there were no skin problems in the pet that was in contact and there were no further problems. The owners have no skin problems. Hills dry cat food was used as food.
As complaints, the owners noted that a few months ago their animal had crusts on the ears, on the muzzle, on the stomach around the nipples. Of the general symptoms, some apathy and slight itching were noted at the sites of lesions on the skin. Antibiotics and corticosteroid hormones (prednisolone) were used as therapy. Against the background of the use of prednisolone, the picture improved somewhat. Twice there was some spontaneous improvement, which lasted for some time, and then the picture resumed.
When examining Tori, it was noted that as lesions at the time of admission, there were crusts on the ears, head, and nipples (photo 4-5). No pustules were found.
The following differential diagnoses were considered as bacterial inflammation of the skin, dermatophytosis, pemphigus (which, from our point of view, was the most likely differential diagnosis).

Research at the time of initial treatment:

• LUM - negative;
• Trichogram - no hair destroyed by dermatophytes;
• Scrapings - negative;
• Smears from under the crust: the result is the presence of acanthocytes (photo 6), neutrophils in large numbers; bacterial flora is absent.

We suggested a biopsy, dermatophyte cultures, trial therapy with the antibiotic cephalexin (25 mg/kg twice daily), and elocom ointment (active ingredient mometasone) on the affected area on the abdomen. The evaluation of such a trial therapy led to the following results: in general, the clinical picture did not change within 14 days. But on the abdomen, where corticosteroid ointment was used, no crusts were observed. Of course, this could mean that we are unlikely to have encountered a bacterial infection.

Dermatophytosis was also not confirmed on the basis of crops. However, after some time we were at an impasse, as the histopathological diagnosis was consistent with pyoderma. The fact is that when we discussed the biopsy with Tori's owners, we assumed that with such a picture, when there are no pustules on the skin, even if it is pemphigus, histology can lead to erroneous results. Therefore, the option of placing the animal in a hospital was proposed, where we would wait for the appearance of pustules on the skin for a high-quality biopsy sampling.
But two aspects did not allow us to lead to such a scenario: firstly, we could not guarantee that the appearance of pustules would happen soon, and, secondly, the owners did not even consider the hypothetical possibility of parting with their pet for some time. Alas, suggesting that owners identify pustules was a utopian idea. In this regard, we settled on the option of tissue sampling with the presence of crusts.
The choice of aggressive therapy is responsible, but we settled on it taking into account the totality of data (history, clinical manifestations, cytology and culture results, results of trial therapy). Despite the fact that histopathology did not confirm our clinical assumptions (Figure 2), we took the liberty of making a diagnosis of pemphigus, which is quite legitimate.
Metipred at doses of 2 mg/kg twice daily was proposed as the drug of choice. During therapy, already at the time of remission, at a decrease in the dose of the drug, a complication arose in the form of a corneal defect (ulcer), which, apparently, was associated with the use of corticosteroids, which usually lead to the activation of protease production in the produced tear. It seems to us that this is precisely what caused such a defect. The recurrence of this problem occurred twice and was eliminated by eye surgery in our clinic, and therefore it was proposed to consider the option of using cyclosporine at a dose of 10 mg/kg/day. As a result, the disease was brought into a long phase of remission, which continues to the present moment (photo 7-9).

AUTOIMMUNE DISEASES OF THE SKIN IN CATS AND DOGS ON THE EXAMPLE OF VELICLES. CAUSES, CLINICAL SIGNS, DIAGNOSIS, TREATMENT

Semenova Anastasia Alexandrovna

2nd year student, Department of Veterinary Medicine and Animal Physiology, KF RGAU-MSHA named after V.I. K.A. Timiryazev, Russian Federation, Kaluga

Beginina Anna Mikhailovna

scientific supervisor, Ph.D. biol. Sciences, Art. Lecturer KF RGAU-MSHA, Russian Federation, Kaluga

As you know, in addition to the usual immunity responsible for protecting the body from foreign elements, there is autoimmunity, which ensures the utilization of old and destroyed cells and tissues of one's own body. But sometimes the immune system begins to "attack" the normal cells and tissues of its own body, resulting in an autoimmune disease.

Autoimmune skin diseases are a very understudied area in veterinary medicine. A small percentage of morbidity causes poor knowledge of these diseases and, as a result, the wrong diagnosis and the choice of the wrong treatment by veterinarians.

One of these diseases are diseases of the pemphigoid complex (pemphigus).

Several types of pemphigus have been found in animals:

Pemphigus foliaceus (PV)

Erythematous pemphigus (EP)

Pemphigus vulgaris

Vegetative pemphigus

Paraneoplastic pemphigus

Hailey-Hailey disease.

The most common in animals are leaf-shaped and erythematous pemphigus.

Pemphigus is an organ-specific autoimmune disease. The pathogenesis of this type of diseases is based on the formation of autoantibodies to tissue and cellular structures of the skin. The type of pemphigus is determined by the predominant type of antibodies.

Causes

The exact causes of this disease have not been fully established. Most veterinarians who have encountered this disease note that severe stress, prolonged exposure to the sun aggravates the course of the disease and, possibly, can also cause pemphigus. Therefore, if symptoms of pemphigus occur, it is recommended to exclude (or minimize) the animal's exposure to the sun.

Some researchers in their articles indicate that pemphigus can be caused by the use of certain drugs, such as Methimazole, Promeris and antibiotics (sulfonamides, Cefalexin). Another common point of view is that the development of the disease can occur as a result of other chronic skin diseases (eg, allergies, dermatitis). However, there is no evidence or research to support this view.

One of the causes of the disease can be identified genetic predisposition. In medicine, a number of studies have been done, during which it was found that the next of kin of a patient with an autoimmune disease has an increased amount of autoantibodies. Based on the fact that some breeds are more susceptible to the disease, it can be concluded that the disease is inherited in animals.

Pemphigus can occur as a result of drug stimulation of the body's genetic predisposition to develop pemphigus.

At the moment, there is no way to find out whether pemphigus is spontaneous or provoked.

Pemphigus foliaceus(Pemphigus foliaceus).

Figure 1. Scheme of the location of lesions on the head in LP

First described in 1977, it occurs in 2% of all skin diseases. Breed predisposition in dogs: Akita, Finnish Spitz, Newfoundland, Chow Chow, Dachshunds, Bearded Collie, Doberman Pinscher. There is no breed predisposition in cats. Animals of middle-aged age get sick more often. No relationship of incidence with gender was noted. In addition to dogs and cats, horses are also affected.

Pemphigus is most often divided into forms according to the causes of occurrence: spontaneous (the greatest predisposition is noted in Akita and Chow Chow) and drug-induced (predisposition is noted in Labradors and Dobermans).

Clinical manifestations. The skin of the back of the nose, ears, crumbs of the feet and the mucous membranes of the mouth and eyes are usually affected. Other parts of the body may also be affected. Lesions in LP are unstable and may progress from erythematous macules to papules, from papules to pustules, then to crusts, and appear intermittently. Damage

Figure 2. Scheme of the location of lesions on the trunk and extremities in LP

accompanied by alopecia and depigmentation of the attacked areas. Of the systemic manifestations, anorexia, hyperthermia, and a depressed state are encountered.

A characteristic feature is large, unrelated follicle pustules (follicle pustules may also be present).

Erythematous (seborrheic) pemphigus(Pemphigus erythematosus)

Mostly dogs of dolichocephalic breeds are ill. Breed or age predisposition of cats is not marked. Lesions are limited, as a rule, to the back of the nose, where erosions, crusts, abrasions, ulcers are found, sometimes pustules and blisters, as well as alopecia and depigmentation of the skin. This type of pemphigus can be considered a milder form of LP. With inappropriate or untimely treatment, it can turn into a leaf-shaped form of pemphigus.

Pathogenesis

Similar in both erythematous and pemphigus foliaceus. The pathogenesis of this is the formation of autoantibodies against surface antigens of epidermal cells, as a result of which immune reactions are activated, leading to acantholysis (breakdown of connections between epidermal cells) and exfoliation of the epidermis. Acantholysis results in vesicles and pustules that often coalesce to form blisters.

Establishing diagnosis

The diagnosis is made on the basis of anamnesis, clinical manifestations, trial antibiotic therapy. However, it is impossible to make an accurate diagnosis of an autoimmune skin disease based only on clinical signs due to the similarity of many dermatological diseases, both autoimmune and immune-mediated diseases, as well as due to the addition of secondary infectious skin diseases. Therefore, it is advised to do more in-depth studies such as cytology and histology to detect and control secondary infectious diseases.

Cytology

This test can be a definitive diagnosis. A characteristic feature of pemphigoid diseases is the presence of a large number of acanthocytes accompanied by neutrophils. Acanthocytes are large cells, 3-5 times the size of neutrophils, also known as acantholytic creatinocytes. Acantholytic creatinocytes are epidermocytes that have lost contact with each other as a result of acantholysis.

Histopathology

In LP, early histopathological signs are intercellular edema of the epidermis and destruction of desmosomes in the lower parts of the germ layer. As a result of the loss of communication between epidermocytes (acantholysis), first gaps are formed, and then bubbles are located under the stratum corneum or granular layer of the epidermis.

With proper biopsy, it is possible to make an accurate diagnosis, as well as to identify secondary infectious diseases. When conducting a biopsy, dermatologists advise taking at least 5 samples. In the absence of pustules, a biopsy of papules or spots should be taken, as they may contain micropustules. Since some diseases are histologically similar to pemphigus (pyoderma, ringworm), Gram stain (for bacteria) and fungal stain (GAS, PAS) should be used.

Repeated studies are done in the absence of a response to treatment, as well as in case of repeated relapse.

In order to make sure that there are no secondary infectious diseases, be sure to do a dermatophyte culture and examine the animal in a Wood's lamp.

Differential diagnoses: Demodicosis, Dermatophytosis, Discoid lupus erythematosus (DLE), Subcorneal pustular dermatosis, Pyoderma, Leishmaniasis, Sebadenitis.

Treatment.

Treatment of autoimmune skin diseases involves modifying or regulating immunological responses through pharmacotherapy. It comes down to achieving remission and maintaining it.

The main drugs are glucocorticoids.

Before choosing this treatment regimen, it is necessary: ​​to keep in mind that the treatment is carried out with glucocorticoids and immunosuppressants, and therefore it is necessary to accurately diagnose and know possible side effects and methods for their prevention; know about the presence of any diseases in the animal, in which treatment with glucocorticoids is contraindicated.

Prednisolone is usually given to dogs at doses of 1 mg/kg every 12 hours. If there is no improvement within 10 days, the dose is increased to 2-3 mg/kg every 12 hours. After achieving remission (approximately after a month or two), the dose is gradually reduced to 0.25-1 mg / kg every 48 hours. Cats are prescribed Prednisolone at doses of 2-6 mg/kg per day, gradually decreasing to a minimum. Prednisolone requires activation in the liver, so it is used only orally.

In about 40% of cases of diseases in dogs, when remission is achieved and the dose is gradually reduced, it is possible to completely cancel the drug, returning to it only during exacerbations.

In veterinary medicine, only five glucocorticoid agents with different dosage forms, duration of action and additional drugs are officially allowed to be used. It must be borne in mind that the treatment is long and in accordance with this, select the drug. It is important to remember that glucocorticoids have a metabolic inhibitory effect on the relationship of the hypothalamus - pituitary - adrenal cortex, which leads to atrophy of the adrenal cortex. Therefore, it is worth choosing a drug with an average duration of the biological effect, so that after achieving remission, with the introduction of the drug every 48 hours, the body has the opportunity to recover, thus reducing the likelihood of complications. For this reason, Prednisolone or Methylprednisolone is usually used, since their duration of biological effect is 12-36 hours.

Methylprednisolone has minimal mineralocorticoid activity, so it is advisable to prescribe it, for example, in the case of polyuria-polydipsia syndrome. This drug is prescribed in doses of 0.8-1.5 mg/kg 2 times a day until remission is achieved, then reduced to a maintenance dose of 0.2-0.5 mg/kg every 48 hours.

Glucocorticoids can increase K + excretion and decrease Na + excretion. Therefore, it is necessary to monitor the state of the kidneys, adrenal glands (due to inhibition of the relationship between the hypothalamus-pituitary-adrenal cortex and subsequent atrophy of the adrenal glands) and control the level of K in the body.

Sometimes the use of glucocorticoids alone is not enough. Therefore, to achieve the best effect, cytostatics are used together with glucocorticoids. The most commonly used dose of azathioprine is 2.2 mg/kg every day or every other day in combination with an adequate dose of glucocorticoid. When remission is achieved, the doses of both drugs are gradually reduced to the minimum effective, which is administered every other day. For cats, Azathioprine is a dangerous drug, because it strongly suppresses the activity of the bone marrow. Instead, Chlorambucil is prescribed in doses of 0.2 mg / kg.

In addition to Azathioprine and Chlorambucil, Cyclophosphamide, Cyclosporine, Cyclophosphamide, Sulfasalazine, etc. are used.

Among the side effects of combined treatment with glucocorticoids and cytostatics, vomiting, diarrhea, suppression of bone marrow function, and pyoderma are distinguished. A hepatotoxic effect may occur due to the toxic effect of azathioprine (the activity of liver enzymes increases), so it is worth using azathioprine with hepatoprotectors. The use of Prednisolone (at doses of 1-2 mg / kg) and Cyclosporine increases the risk of tumors.

Chrysotherapy (treatment with gold preparations) is also used in the treatment of pemphigus. According to American researchers, it is effective in 23% of cases in dogs and in 40% of cases in cats. Used as monotherapy with gold salts, and in combination with chrysotherapy with glucocorticoids.

Myocrysin is administered intramuscularly at initial doses of 1 mg (for cats and dogs weighing less than 10 kg) and 5 mg (for animals weighing over 10 kg) once a week. The dose is doubled if there are no side effects within seven days. In the absence of side effects, treatment is continued at doses of 1 mg/kg once a week.

In addition to Myokrizin, the use of the drug Auranofin is described in veterinary medicine. It has fewer side effects and is more suitable for long-term treatment, because. is administered orally. Use Auranofin in doses of 0.02-0.5 mg/kg every 12 hours orally. The drug is more easily tolerated by animals, side effects are less common.

Forecast in these diseases is unfavorable. More often, if left untreated, it is fatal. The prognosis for drug-induced pemphigus may be positive with discontinuation of the drug and a short course of immunosuppressants.

There are cases in which, after discontinuation of drugs, remission lasted more than one year and even for life. According to studies at the University of Pennsylvania, 10% of cases of disease in dogs ended in long-term remission after drug withdrawal. Similar results were obtained by scientists at the University of North Carolina. Other researchers noted long-term remission after discontinuation of drugs in 40-70% of cases.

The highest mortality rate (90%) was found in patients during the first year of the disease.

Cats have a better prognosis for this disease than dogs. Cats with pemphigus have a higher survival rate and fewer cats relapse after all drugs are stopped.

Private clinical case

Anamnesis . Dog breed Black Russian Terrier, 45 kg. The first symptoms appeared at the age of 7. First, the mucous membranes of the eyes became inflamed, then, after a few days, the dog refused to eat. Inflammation of the gums was found. At the same time, lesions (pustules) appeared on the crumbs of the paws and the bridge of the nose. An increase in temperature and a depressed state of the animal were noted.

Cytological and histological studies of pustules taken from the crumbs of the paws and the back of the nose were carried out. As a result, a diagnosis of Pemphigus foliaceus was made.

Prednisolone was used for treatment at a dose of 25 mg every 24 hours for 4 days. Then within a week the dose was increased to 45 mg. Prednisolone was co-administered with Potassium Orotate (500 mg) orally. A week later, the dose of Prednisolone was gradually (over two weeks) reduced to 5 mg every 24 hours. And then, after 3 months - up to 5 mg - every 48 hours. Locally, for the treatment of skin areas damaged by pustules, tampons moistened with Miramistin solution were used, after drying in air - Terramycin spray, followed by application of Akriderm Genta ointment. At the same time, protective bandages and special shoes were used constantly, until the paw pads were completely healed. Due to the regular occurrence of symptoms such as alopecia, depigmentation, the appearance of erythematous spots, etc., vitamin E (100 mg 1 time per day) was prescribed. As a result of this treatment, a stable remission was achieved within a year and a half. The dog is under supervision.

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Origin mechanisms

Autoimmune pathology can be characterized as an attack of the immune system against the organs and tissues of the body, resulting in their structural and functional damage. The antigens involved in the reaction, usually present in a person or animal and characteristic of them, are called autoantigens, and antibodies capable of reacting with them are called autoantibodies.

Autoimmunization of the body is closely related to the violation of immune tolerance, i.e. the state of unresponsiveness of the immune system in relation to the antigens of its organs and tissues.

The mechanism of autoimmune processes and diseases is similar to the mechanism of immediate and delayed types of allergy and is reduced to the formation of autoantibodies, immune complexes and sensitized T-lymphocytes-killers. Both mechanisms can be combined or one of them predominates.

The essence of autoimmune processes lies in the fact that under the influence of pathogens of infectious and parasitic diseases, chemicals, drugs, burns, ionizing radiation, feed toxins, the antigenic structure of organs and tissues of the body changes. The resulting autoantigens stimulate the synthesis of autoantibodies in the immune system and the formation of sensitized T-lymphocytes-killers capable of carrying out aggression against altered and normal organs, causing damage to the liver, kidneys, heart, brain, joints and other organs.

Morphological changes in autoimmune diseases are characterized by inflammatory and degenerative changes in damaged organs. Parenchyma cells show granular dystrophy and necrosis. In the blood vessels, mucoid and fibrinoid swelling and necrosis of their walls, thrombosis are noted, lymphocytic-macrophage and plasmacytic infiltrates are formed around the vessels. In the connective tissue of the stroma of the organs, dystrophy in the form of mucoid and fibrinoid swelling, necrosis and sclerosis are detected. Hyperplasia, intensive infiltration by lymphocytes, macrophages and plasma cells are expressed in the spleen and lymph nodes.

Autoimmune reactions play an important role in the pathogenesis of many animal and human diseases. The study of autoimmune processes is of great practical interest. The study of autoimmunity has led to significant advances in the diagnosis and therapy of a number of human and animal diseases.

There is a certain spectrum of manifestations of autoimmune pathology.

Some are characterized by organ damage - organ specificity. An example is Hashimoto's disease (autoimmune thyroiditis), in which specific lesions of the thyroid gland are observed, including mononuclear infiltration, destruction of follicular cells and the formation of germinal centers, accompanied by the appearance of circulating antibodies to certain components of the thyroid gland.

Generalized or non-organ-specific are characterized by an autoimmune reaction with antigens common to various organs and tissues, in particular, with antigens of the cell nucleus. An example of such a pathology is systemic lupus erythematosus, in which autoantibodies do not have organ specificity. Pathological changes in these cases affect many organs and are mainly connective tissue lesions with fibrinoid necrosis. The blood cells are also often affected.

At the same time, the autoimmune response to self antigens with the participation of cellular and humoral immunity is primarily aimed at binding, neutralizing and eliminating old, destroyed cells, products of tissue metabolism from the body. Under conditions of a normal physiological state, the degree of possibility of autoimmune processes is strictly controlled.

Signs of autoimmune pathology, when autoimmune homeostasis is disturbed, may be the appearance of barrier antigens from tissues such as the lens of the eye, nervous tissue, testicles, thyroid gland, antigens that appeared under the influence of inadequate influences on the body of environmental factors of infectious or non-infectious origin, genetically determined defects in immunocytes . Sensitization to autoantigens develops. Autoantibodies interacting with them can be conditionally divided into several groups: autoantibodies that cause cell damage, which underlies autoimmune diseases; autoantibodies themselves do not cause, but aggravate the course of an already existing disease (myocardial infarction, pancreatitis, and others); autoantibodies are witnesses that do not play a significant role in the pathogenesis of the disease, but an increase in the titer of which may be of diagnostic value.

Diseases associated with tissue damage by autoantibodies may be due to:

• antigens;
• antibodies;
• pathology of the organs of immunogenesis.

Autoimmune pathology caused by antigens

A feature of this pathology is that the tissues of one's own body, either without changes in their antigenic composition, or after its change under the influence of environmental factors, are perceived by the immunological apparatus as alien.

When characterizing the tissues of the first group (nervous, lens of the eye, testicles, thyroid gland), two cardinal features should be noted: 1) they are laid down later than the immune apparatus, and therefore immunocompetent cells are preserved for them (unlike tissues that are laid down before the immune apparatus and secrete factors destroying immunocompetent cells to them); 2) the peculiarities of the blood supply of these organs are such that the products of their degradation do not enter the bloodstream and do not reach the immunocompetent cells. When the hematoparenchymal barriers are damaged (trauma, surgery), these primary antigens enter the bloodstream, stimulate the production of antibodies that, penetrating through the damaged barriers, act on the organ.

For the second group of autoantigens, it is decisive that under the influence of an external factor (infectious or non-infectious nature) the tissue changes its antigenic composition and actually becomes alien to the body.

Autoimmune pathology caused by antibodies

Has several options:

• The foreign antigen that enters the body has determinants similar to the antigens of the body's own tissues, and therefore the antibodies formed against the foreign antigen "mistake" and begin to damage their own tissues. The foreign antigen may be absent in the future.
• A foreign hapten enters the body, which combines with the protein of the body, and antibodies are produced against this complex that can react with each of its individual components, including its own protein, even in the absence of a hapten.
• The reaction is similar to type 2, only a foreign protein enters the body, reacting with the hapten of the body and antibodies produced against the complex continue to react with the hapten even after the foreign protein is removed from the body.

Autoimmune pathology caused by organs of immunogenesis

The immune apparatus does not contain immunocompetent cells to the tissues of one's own body, which are laid in embryogenesis before the immune system. However, such cells can appear during the life of the organism as a result of mutations. Normally, they are either destroyed or suppressed by suppressor mechanisms.

According to etiopathogenesis, autoimmune pathology is divided into primary and secondary. Autoimmune diseases are primary.

Autoimmune diseases include diabetes, chronic thyroiditis, atrophic gastritis, ulcerative colitis, primary liver cirrhosis, orchitis, polyneuritis, rheumatic heart disease, glomerulonephritis, rheumatoid arthritis, dermatomyositis, hemolytic anemia.

The pathogenesis of primary autoimmune pathology in humans and animals is directly related to genetic factors that determine the nature, location, and severity of their accompanying manifestations. The main role in the determination of autoimmune diseases is played by genes encoding the intensity and nature of immune responses to antigens - genes of the major histocompatibility complex and immunoglobulin genes.

Autoimmune diseases can be formed with the participation of various types of immunological damage, their combination and sequence. The cytotoxic effect of sensitized lymphocytes (primary cirrhosis, ulcerative colitis), mutant immunocytes that perceive normal tissue structures as antigens (hemolytic anemia, systemic lupus erythematosus, rheumatoid arthritis), cytotoxic antibodies (thyroiditis, cytolytic anemia), antigen-antibody immune complexes may prevail. (nephropathy, autoimmune skin pathology).

Acquired autoimmune pathology is also registered in diseases of a non-infectious nature. An increased immunological reactivity of horses with extensive wounds is known. In cattle, ketosis, chronic feed poisoning, metabolic disorders, beriberi induce autoimmune processes. In young newborns, they can occur by the colostral route, when autoantibodies and sensitized lymphocytes are transmitted through colostrum from sick mothers.

In radiation pathology, a large, even leading role is assigned to autoimmune processes. Due to a sharp increase in the permeability of biological barriers, tissue cells, pathologically altered proteins and substances associated with them, which become autoantigens, enter the bloodstream.

The production of autoantibodies occurs with any type of irradiation: single and multiple, external and internal, total and local. The rate of their appearance in the blood is much higher than antibodies to foreign antigens, since the body always has the production of normal anti-tissue autoantibodies that play an important role in binding and removing soluble metabolic products and cell death. The production of autoantibodies is even higher with repeated exposure to radiation, that is, it obeys the usual patterns of primary and secondary immune responses.

Autoantibodies not only circulate in the blood, but at the end of the latent period, and especially during the height of radiation sickness, they bind so strongly to the tissues of internal organs (liver, kidneys, spleen, intestines) that they cannot be removed even by repeated washing of finely divided tissue. .

Autoantigens that can induce autoimmune processes are also formed under the influence of high and low temperatures, a variety of chemicals, as well as some drugs used to treat animals.

Autoimmunity of bulls and reproductive functions

The concentration of the best sires at state breeding enterprises and the use of their semen in artificial insemination has significantly increased the genetic potential of dairy herds. In conditions of widespread use of male sires, the assessment of the quality of their semen is of great importance.

In cases of autoimmunity to their own semen in males with normal ejaculates in other respects, there is a decrease in the fertilizing ability of the seed and the embryonic survival of their offspring.

Immunological studies of the reproductive ability of breeding males revealed that overheating of the testes causes a violation of spermatogenesis, accompanied by the appearance of autoantibodies in the blood, and that their effect is due to an increase in the permeability of the blood-testicular barrier.

There is also evidence that with age in sires, partial hyaline degeneration of the basement membrane, necrosis, and slippage of the seminal epithelium appear in some convoluted tubules of the testis.

Circulating antibodies to autologous spermatozoa do not always and immediately inhibit spermatogenesis due to the presence of a powerful hematotesticular barrier between blood and seminal epithelial cells. However, trauma, prolonged overheating of the testes and the whole organism, as well as experimental active immunization, weaken this barrier, which leads to the penetration of antibodies into Sertoli cells and spermatogenic epithelium and, as a result, to disruption or complete cessation of spermatogenesis. Most often, the process stops at the stage of round spermatids, but after a long action of antibodies, the division of spermatogonia also stops.

Experimental autoimmune diseases

For a long time, the attention of doctors and biologists has been attracted by the question of whether sensitization against one's own tissue components can be the cause of the disease. Experiments to obtain autosensitization were carried out on animals.

It has been found that intravenous administration of a foreign brain suspension to a rabbit induces the formation of brain-specific antibodies that are able to specifically react with brain suspension, but not other organs. These anti-brain antibodies cross-react with brain suspensions from other animal species, including the rabbit. The animal producing the antibodies showed no pathological changes in its own brain. However, the use of Freund's adjuvant changed the observed picture. Brain suspensions mixed with complete Freund's adjuvant, after intradermal or intramuscular administration, in many cases cause paralysis and death of the animal. Histological examination revealed areas of infiltration in the brain, consisting of lymphocytes, plasma and other cells. Interestingly, intravenous injection of rabbit brain suspension into rabbits (animals of the same species) cannot induce the formation of autoantibodies. However, rabbit brain suspension mixed with Freund's adjuvant causes autosensitization to the same extent as any foreign brain suspension. In other words, brain suspensions under certain conditions can be self-antigens, and the disease caused can be called allergic encephalitis. Some researchers believe that multiple sclerosis may be caused by autosensitization to certain brain antigens.

Another protein has organ-specific properties - thyroglobulin. Intravenous injection of thyroglobulin obtained from other animal species resulted in the production of thyroglobulin-precipitating antibodies. There is a great similarity in the histological picture of experimental rabbit thyroiditis and chronic thyroiditis in humans.

Circulating organ-specific antibodies are found in many diseases: anti-renal antibodies in kidney diseases, anti-cardiac antibodies in certain heart diseases, and so on.

The following criteria have been established that may be useful when considering diseases caused by autosensitization:

• direct detection of free circulating or cellular antibodies;
• identifying the specific antigen against which the antibody is directed;
• development of antibodies against the same antigen in experimental animals;
• the appearance of pathological changes in the corresponding tissues in actively sensitized animals;
• obtaining a disease in normal animals by passive transfer of serum containing antibodies or immunologically competent cells.

A few years ago, when breeding pure lines, a strain of chickens with hereditary hypothyroidism was obtained. Chicks spontaneously develop severe chronic thyroiditis and their serum contains circulating antibodies to thyroglobulin. Searches for a virus have so far been unsuccessful, and it is very possible that there is a spontaneously observed autoimmune disease in animals. Antireceptor autoantibodies and their significance
in pathology

Autoantibodies to receptors of various hormones are well studied in some types of endocrine pathology, in particular in diabetes, thyrotoxicosis, which allows many researchers to consider them as one of the leading links in the pathogenesis of diseases of the endocrine glands. Along with this, in recent years, interest has grown in other antireceptor autoantibodies - antibodies to neurotransmitters, their participation in the regulation of the function of the cholinergic and adrenergic systems of the body has been proven, and their connection with certain types of pathology has been established.

Studies of the nature of atopic diseases, conducted over several decades, have undeniably proved the immunological nature of their triggering mechanism - the role of IgE in the mechanism of the release of biologically active substances from mast cells. But only in recent years have more complete data been obtained on the immune nature of disorders in atopic diseases, concerning not only the trigger mechanism of allergies, but also the atopic syndrome complex associated with impaired functioning of adrenergic receptors in these diseases, and in particular in asthma. We are talking about establishing the fact of the existence of autoantibodies to b-receptors in atopic asthma, which puts this disease in the category of autoimmune pathology.

The question of the cause and mechanism of the production of autoantibodies to the b-receptor remains open, although, based on general ideas about the development of allergic diseases, the appearance of autoantibodies can be explained as a consequence of dysfunctions of suppressor cells, or, based on Jerne's theory, by the fact that autoimmunity is the normal physiological state of the immune system and that physiological autoantibodies under the influence of external or internal conditions turn into pathological ones and cause classic autoimmune pathology.

Unlike autoantibodies to β-adrenergic receptors, which are currently insufficiently studied, autoantibodies to acetycholine receptors have been studied quite well both in the experiment and in the clinic. There is a special experimental model showing an important pathogenetic autoantibodies to acetylcholine receptors - experimental myasthenia gravis. Immunization of rabbits with acetylcholine receptor preparations can cause a disease resembling human myasthenia gravis. In parallel with the increase in the level of acetycholine antibodies, weakness develops in animals, resembling myasthenia gravis in many clinical and electrophysiological manifestations. The disease proceeds in two phases: acute, during which cell infiltration and antibody damage occur, and chronic. The acute phase may be caused by passive transfer of IgG from immunized animals.

Autoallergy

Under various pathological conditions, blood and tissue proteins can acquire allergenic properties that are foreign to the body. Autoallergic diseases include allergic encephalitis and allergic collagenases.

Allergic encephalitis occurs when repeated administration of various kinds of extracts obtained from the brain tissue of all adult mammals (excluding rats), as well as from the brain of chickens.

Allergic collagenases represent a peculiar form of infectious autoallergic diseases. The autoantibodies formed in these cases cause a cytotoxic effect in the tissues; there is a lesion of the extracellular part of the connective tissue of a collagenous nature.

Allergic collagenases include acute articular rheumatism, some forms of glomerulonephritis, etc. Corresponding antibodies were found in acute articular rheumatism. As a result of experimental studies, the allergic nature of acute articular rheumatism was proved.

Many researchers believe that the pathogenesis of rheumatic heart disease is similar to the pathogenesis of rheumatic heart disease. Both of them develop against the background of focal streptococcal infection. In the experiment, when animals were injected with chromic acid, they developed renal autoantibodies and glomerulonephritis. Autoantibodies - nephrotoxins that damage the kidney tissue can be obtained by freezing the kidneys, by ligating the renal vessels, ureters, etc.

Literature:

• Pathological physiology of the immune system of domestic animals. St. Petersburg, 1998
• Chebotkevich V.N. Autoimmune diseases and methods of their modeling. St. Petersburg, 1998
• Immunomorphology and immunopathology. Vitebsk, 1996.
• "Zootechnia" - 1989, No. 5.
• "Livestock" -1982, No. 7.
• Reports of VASKhNIL - 1988, No. 12.
• Autoantibodies of the irradiated organism. Moscow: Atomizdat, 1972.
• Modern problems of immunology and immunopathology. "Medicine", Leningrad branch, 1970.
• Ilyichevich N.V. Antibodies and regulation of body functions. Kiev: Naukova Dumka, 1986

The diseases of this group are the result of the inability of the immune system to distinguish between “self” and “foreign”. As a result, the body produces autoantibodies, that is, antibodies against the tissues of its own body. Some of these diseases are known as "immune-mediated", they develop due to the formation of antigen-antibody complexes. Autoimmune diseases can be triggered by bacteria, viruses, drugs, tumors, and possibly vaccinations.

YOGA is the most common among all diseases of the immune system in dogs. In this disease, the immune system attacks and destroys the body's own red blood cells. Such a reaction can be triggered by viruses, drugs, possibly vaccinations, and even cancer. The disease can develop suddenly and quickly turn into an acute stage, but it can be chronic. The more red blood cells are destroyed, the worse the prognosis.

With acute development of YOGA, the dog is in a depressed state, within one to three days he may experience fever, shortness of breath, the color of the gums is pale pink, the color of the urine is dark. Difficulties in movement may occur. In the chronic form, the disease proceeds in the form of remissions and relapses.

Diagnosis and treatment. Diagnosis of YOGA is based on clinical signs and blood test results. It is vital to start treatment as soon as possible with corticosteroids or other drugs that suppress the activity of the immune system. Blood transfusions are controversial, not only because an overactive immune system will destroy fresh red blood cells, but because it sometimes even worsens a dog's condition. But there are rare situations in which a blood transfusion is the only way to keep a dog alive.

The term "thrombocytopenia" means a reduced amount of small cells called platelets, or platelets, in the blood. Platelets are involved in blood clotting, so their deficiency can cause bleeding and bruising for any reason.

IOT is more common in females, regardless of whether the dog is spayed or not. This condition can develop after an infection, or as a result of an immune system reaction to certain medications. The first sign may be a bruise, accidentally noticed on an area of ​​\u200b\u200bthe body with less thick hair. The affected dog's stool is usually black due to bleeding in the gastrointestinal tract, and blood is also present in the urine. Some dogs experience nosebleeds.

Diagnosis and treatment of IOT. The veterinarian should differentiate thrombocytopenia from hemolytic anemia or other bleeding disorder. It is necessary to conduct an accurate count of platelets per unit volume of blood. Treatment is usually with corticosteroids. Sometimes blood and platelet transfusions are used, in combination with drugs that suppress the activity of the immune system. As with immune-mediated hemolytic anemia, some dogs develop a chronic form of the disease that requires long-term treatment with drugs that suppress the activity of the immune system.

Neutropenia is low levels of neutrophils (a type of white blood cell) in the blood. Some drugs, such as sulfonamides and anticonvulsants, can cause a condition in which the immune system suppresses the production of neutrophils. The disease responds well to treatment with corticosteroids.

This form of arthritis develops due to the formation of antigen-antibody complexes on the synovium. Such arthritis may be accompanied by inflammation of the muscles (polymyositis) or inflammation of the nerve endings (polyneuritis). All forms of immune-mediated arthritis are treated with corticosteroids and other drugs that suppress the activity of the immune system. Some dogs with rheumatoid arthritis require surgery and stabilization of the affected joint.

This rare disease - inflammation of the membranes and blood vessels of the brain and spinal cord - may be associated with the formation of immune complexes. It is observed in young dogs of breeds: Akita, Beagle, Bernese Mountain Dog, Boxer, German Pointer. The dog suffers from intermittent pain in the neck, moves reluctantly. Seizures last about a week. The use of corticosteroids alleviates the course of the disease.

Some autoimmune diseases affect skin cells. Solar dermatitis, also called discoid lupus or erythematosus, is the most common. It occurs more frequently in dogs of certain breeds living in sunny climates than in others. The condition is known as "collie nose" because collies (smooth-haired and long-haired) and shelties are most susceptible to it. White American Shepherd and Siberian Husky breeds are also at risk for this condition.

Diagnosis and treatment. The diagnosis is established by visual examination. It responds well to treatment with corticosteroids, it is necessary to use measures of protection from sunlight.

These diseases are rare. The most common of them is pemphigus foliaceus; initially resembles allergic dermatitis with the development of a secondary bacterial infection affecting the face, nose, ears and skin around the eyes. Systemic (or acute) lupus erythematosus can cause similar skin problems and, in addition, affect internal organs. Other autoimmune skin diseases are also observed in dogs, such as infectious-allergic and toxic-allergic exudative erythema, toxic-allergic epidermal necrolysis, and hereditary dermatomyositis.