Pemphigus foliaceus in dogs and cats. Methods for determining and treating the type of pemphigus in dogs

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 medicines. 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

Among the possible side effects in dogs, anemia, leukopenia, thrombocytopenia, pancreatitis can form. In this regard, on initial stage every 14 days (for 2 months), then every 30 days (for 2 months), and finally every 3 months, the entire period of giving azathioprine should be monitored for clinical and biochemical parameters blood in dogs. In general, if we talk about state control general health patients treated for pemphigus should be aware that every 6 months, all those who are given glucocorticoids require a routine examination. It includes clinical and biochemical analysis blood, clinical analysis urine and 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. As aids therapy in dogs, vitamin E can be used in doses of 400-800 IU 2 times a day and indispensable fatty acid 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 diseases. skin diseases such as discoid lupus erythematosus, lupus onychodystrophy, metatarsal fistula 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 after a few months, the drugs begin to be reduced - first to a double dose, and then to a single daily dose. Side effects rare and usually associated with the use of niacinamide. These include vomiting, anorexia, drowsiness, diarrhea, and elevated serum liver enzymes. Tetracycline may reduce 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:

Clinical Cases 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 summer period happens in the country, there are no contacts with other animals, the owners have no 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 trial antibiotic therapy, but to arrive at the appointment after the end of the effect of the convenia drug (cefovecin - a cephalosporin of the 3rd generation) to conduct preliminary crops in order to select antibacterial drug. The owners agreed only to conduct a biopsy, unfortunately, without accepting our other proposals, and in order to further treatment returned to their doctor. 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. O future fate this patient we do not know.

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 have a cat with early age, the animal had no skin problems at the time of purchase. There was contact with 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. From common symptoms there was some apathy and slight itching in the 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.
Differential diagnoses were considered as bacterial inflammation skin, dermatophytosis, pemphigus (was the most likely, from our point of view, 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 in large numbers; bacterial flora is absent.

One of the reasons for the attack of the cells of the body by its own lymphocytes can be the similar structure of the cells of the body itself with the antigens of a bacterium or virus, i.e. the lymphocyte "confuses" its own cells with the antigens of infectious agents.

Typically, a tendency to autoimmune pathology is genetic. Predisposing factors can be UV radiation, infections, uncontrolled and unreasonable use of immunostimulating agents, exposure to any chemicals.

The nature of autoimmune diseases in cats is not yet well understood. With pemphigus, disturbances in the functioning of the animal's immune system lead to an attack on its own cells of the epidermis. The destruction of skin cells and the release of their contents is clinically manifested by the formation of blisters.

One of the reasons for the attack of the cells of the body by its own lymphocytes can be the similar structure of the cells of the body itself with the antigens of a bacterium or virus, i.e. the lymphocyte "confuses" its own cells with the antigens of infectious agents.

The second reason may be a violation of screening of autoreactive lymphocytes at the stage of their maturation. If a lymphocyte at the stage of maturation is not able to distinguish host cells from foreign antigens, then such a lymphocyte must be destroyed. Sometimes the destruction mechanisms are violated.

Autoimmune antibodies: the body produces antibodies that attack healthy tissues and cells as if they were pathogenic.

Prolonged exposure to the sun.

Some breeds may have a hereditary predisposition.

Types of pemphigus

4 types of pemphigus are known, hitting dogs pemphigus foliaceus, pemphigus erythematous, pemphigus vulgaris and pemphigus vegetative.

In pemphigus foliaceus, autoantibodies are found in the outermost layers of the epidermis and blisters begin to form on the healthy skin. Erythematous pemphigus proceeds in almost the same way as leaf-shaped, but less painful.

Pemphigus vulgaris is characterized by the formation of deeper ulcers, as antibodies accumulate in the lower layers of the epidermis. As for vegetative pemphigus, it affects only dogs and is considered the rarest variety.

Vegetative pemphigus resembles pemphigus vulgaris, but is much milder with the formation of less painful ulcers.

Clinical signs

Since exfoliative pemphigus is most common in cats, we first look at the symptoms of this type of disease:

• Generalized pustular eruptions (pictured), multiple crusts, small ulcers, redness and itching of the skin, with the head, ears and groin most often affected.

• In other cases, large papules filled with a cloudy liquid are observed.

• Large cysts often form in the thickness of the skin.

• AT severe cases gums are also involved in the process, as a result of which problems with teeth begin (up to their loss).

• Similarly, the process involves nail beds, the claws of the animal begin to stagger, sometimes fall out. The process is very painful, gives the animal severe suffering.

• bloated The lymph nodes, when they are probed, the cat clearly shows signs of displeasure. The animal becomes lethargic, fever and lameness increase (if the claws are involved in the process). Note that all these signs are characteristic only for the severe course of the process.

• Secondary bacterial infection possible due to the contamination of pyogenic microflora of opened papules and ulcers.

Autoimmune diseases- a group of diseases that are characterized by an excessive reaction of the immune system to the body's own cells and tissues, the so-called target cells. In dogs and cats of autoimmune origin include diseases of the pemphigoid complex (pemphigus foliaceus, bullous pemphigoid, vegetative and erythematous pemphigus), systemic, discoid lupus erythematosus, auricular polychondritis, vasculitis, cold agglutinin disease,.

Pemphigus foliaceus

In this disease, the target cells are intercellular substance in . As a result, splitting occurs between the papillary and stratum corneum. Externally this process manifested by education. Pustules are usually localized in the area of ​​the muzzle and auricles, large in size, symmetrically located. In the absence of pustules, a misdiagnosis is often made. Systemic reactions can be observed - anorexia, fever, apathy. The diagnosis is confirmed with .

Pemphigus vulgaris

With this disease, splitting occurs mainly between the basal and stratum corneum of the epidermis. Clinically, pemphigus vulgaris presents with vesicles and mucosal ulcerations. oral cavity and mucocutaneous border. Since pemphigus vulgaris occurs with the appearance of ulcers in, the disease is often severe and can threaten the life of the animal. If you suspect pemphigus vulgaris feline calicivirus and ulcerative gingivitis should be excluded. Diagnosis is based on histological examination of the skin. For this disease characterized by the presence of plasma cells on the basement membrane, which are located in the form of "tombstones".

bullous pemphigoid

It occurs in dogs, but not in cats. It is manifested by the appearance of short-term blisters with purulent contents, then they ulcerate. Lesions are localized on the muzzle, mucocutaneous border, on the abdomen, in inguinal region, limbs. The analysis is based on a biopsy of lesions.

Vegetative pemphigus

It is extremely rare. It appears in a milder form than other forms of pemphigus (multiple papules and pustules). It is important to exclude skin neoplasms. Diagnostics includes histological examination skin.

Erythematous pemphigus

Counts mild form pemphigus. Often lesions are localized only in the nose. There is depigmentation of the nose, crusts, ulcers, blisters on the back of the nose and in the region of the bridge of the nose.

With all types of pemphigus, there may be positive symptom Nikolsky. Outwardly, it is manifested by desquamation of the epithelium at the slightest touch. This is due to the fact that delamination of the epidermis occurs and the connection between the layers is broken.

Systemic lupus erythematosus

In this disease, antinuclear antibodies are produced that affect the cells of all body systems - blood, joints, skeletal muscles, lungs, kidneys, organs gastrointestinal tract, skin, central nervous system. Unlike systemic lupus erythematosus, discoid lupus erythematosus primarily affects the skin.
With lupus skin lesions usually symmetrical, localized on the muzzle - nose, auricles, periorbital region, mucocutaneous border. First, there are foci of depigmentation, then erythema appears and subsequently ulceration of the skin in this area occurs. In systemic lupus erythematosus, there are the following symptoms: hemolytic anemia, thrombocytopenia, fever, polyarthritis.

For the diagnosis of lupus, there are specific tests - a test for antinuclear antibodies and a test for lupus erythematosus. Also, with deep dermatoses, a skin biopsy is informative. If systemic lupus erythematosus is suspected, complex diagnostics to assess the involvement of other organs and systems in pathological process.

Auricular polychondritis

The target cells in this disease are cartilage cells. Anti-collagen antibodies are formed in the body. Outwardly, the disease manifests itself mainly by damage to the auricles - swelling, soreness, redness occur, which, if left untreated, leads to deformation of the cartilage tissues. Fever and lesions of the connective tissues of the nasal passages may also be noted. A biopsy of the affected tissue is required to confirm the diagnosis.

Vasculitis

When amazed blood vessels, the disease causes narrowing of the lumen of the vessels. Due to insufficient blood supply gradually tissue death occurs in the peripheral parts of the body. Most often, the edges of the auricles, paw pads, the tip of the tail, scrotum, and lips are affected. Diagnosis is based on clinical signs and confirmed by skin biopsy.

cold agglutinin disease

The disease is based on Ig M on erythrocytes. It is characteristic that erythrocytes react with immunoglobulins only when the temperature drops. Thus, the disease manifests itself more often in the cold season, the distal parts of the body are affected: ears, limbs, nose, tail, scrotum. There is depigmentation in these areas, the development of necrosis is possible.

Vitiligo

Melanocytes in the epidermis are affected. Outwardly, it manifests itself as a loss of pigment in various parts of the body. The area of ​​the nose, lips, and paw pads are mainly affected. predisposed to disease Siamese cats. Effective treatment in this moment not developed. Spontaneous return of the pigment may occur.

Treatment

Treatment of all autoimmune dermatoses in cats and dogs other than vitiligo is based on immunosuppressive therapy. For this, drugs are prescribed, cyclosporine, azathioprine, chlorambucil. The drugs are used both individually and in combination. In addition to immunosuppressive therapy, symptomatic treatment- antibiotic therapy in case of layering of secondary microflora, drugs that improve peripheral blood supply in vasculitis.
The prognosis for autoimmune dermatoses depends on the involvement of other organs and systems in the pathological process. It is important to start treatment as early as possible, this increases the chances of a successful outcome, which is why it is so important to make an appointment with a doctor in a timely manner. veterinarian and do not self-medicate your pet.

Paul B Bloom 1.2
1. Clinic of Allergology, Skin and Ear Diseases of Pets, Livonia, USA
2. Department of Small Animal Clinical Veterinary Medicine, Department of Dermatology, Michigan State University, USA

Diagnosis of any skin disease is based on a thorough history taking, clinical manifestations(primary localization, nature and distribution of elements), laboratory tests and response to treatment. The most valuable laboratory technique for autoimmune skin lesions is histological examination. But even this can lead to confusion if tissue samples are taken inappropriately.

Pemphigus (pemphigus)

With pemphigus the immune system mistakenly attacks desmosomes. Desmosomes are point-to-cell contacts connecting, in particular, keratinocytes.

Pemphigus exfoliative (EP) is the most common form of pemphigus and probably the most commonly diagnosed autoimmune disease skin in dogs and cats. Other forms of pemphigus encountered in practice include pemphigus erythematous and panepidermal pemphigus. Basically, EP affects young and adult animals with an average age of onset of 4 years. Sixty-five percent of dogs become ill before the age of 5. EP has been described in many breeds, but the author's experience shows that increased risk occurrence of this disease in Chow Chow and Akita. There was no relationship between incidence and gender.

Three forms of EP are described in the literature - spontaneous pemphigus, drug-associated (both drug-induced and drug-induced) and a form associated with chronic disease skin, but the latter is extremely rare in practice. This observation is based on the experience of the author, and there is no evidence for it. The vast majority of cases are spontaneously occurring disease.

When taking the history, the owner may report that the features wax and wane, that the progression of the disease was slow (especially in cases with localization exclusively on the face), or that the features appeared acutely (most often with a generalized lesion). With generalization, dogs often have a fever, swelling of the limbs and common features. Itching in any form may be absent, and may be moderate.

There are three patterns of primary spread of EP:

1. facial form (the most common), in which the bridge of the nose, nose, periorbital zone, auricles are affected (especially in cats);
2. plantar form (only paronychia can be observed in cats);
3. a generalized form in which elements appear on the muzzle and then spread (note - in dogs, elements sometimes appear all over the body at once).

Elements go through the following stages of development: erythematous spot pustule annular ridge (“collar”) erosion yellow-brown crust. Because of the involvement hair follicles often there is a multifocal or diffuse alopecia.

The primary element of EP are large pustules not associated with follicles (pustules are also present in the follicles) most often on the bridge of the nose, paw pads, nose and auricles(in cats, elements can be localized around the nipples). By comparison, pustules in bacterial pyoderma are localized in follicles, located on the abdomen and/or trunk, and are much smaller. Secondary elements in cats and dogs are observed much more often. These include epidermal collars, yellow-brown crusts, and erosions. They may be accompanied systemic lesion, distal limb edema, fever, drowsiness and lymphadenopathy.

The differential range includes any disease with pustules, crusts, and scaling, eg, pemphigus erythematosus, zinc-deficient dermatosis (especially with involvement of the paw pads), metabolic epidermal necrosis (especially with involvement of the paw pads), bacterial and fungal (dermatophytosis) infections, and demodicosis. , discoid lupus erythematosus (DLE) (facial / nasal form), erythema multiforme, mycosis, leishmaniasis and inflammation of the sebaceous glands.

Diagnostics

A cytological preparation of a pustule or crust should be made. Microscopy will show acantholytic keratinocytes, either single or in clusters, surrounded by normal neutrophils and/or eosinophils in the absence of bacteria. The only method confirming pemphigus is histology. A biopsy should be taken from an intact pustule or, in its absence, from a crust. Proteases of bacteria (with pyoderma) or dermatophytes (Trichophyton mentagrophytes) destroy intercellular glycoproteins (desmoglein), leading to acantholysis. Since these infectious diseases very similar to EP histologically, a specific stain for both bacteria (Gram) and fungi (GMS, PAS) should be used when making a biopsy diagnosis. The author routinely performs dermatophyte cultures in all cases of suspected EP.

Forecast

EN can be caused or provoked by drugs (in the latter case, the latent disease is detected by a reaction to the drug). Drug-induced EN resolves after discontinuation of the drug and a short course of immunosuppressants.

Drug-induced EN occurs when a drug stimulates genetic predisposition organism to the development of EP. Usually this form of EN should be treated as idiopathic EN. There is currently no way to determine whether drug-associated EN is drug-induced or drug-induced. In fact, there is no test to predict how well EN will respond to treatment other than the treatment itself.

A study at the University of North Carolina (USA) found that six out of 51 dogs with EN were able to stop all treatment, after which remission lasted more than 1 year. The author has seen many cases (not drug-associated) in which long-term (lifelong) remission was achieved by slow withdrawal of drugs. This clinical observation is supported by a recent study in which 6 of 51 dogs with EN were able to achieve long-term remission without medication. Interestingly, these dogs were from high exposure areas. ultraviolet radiation(North Carolina or Sweden).

In this group of dogs, it took 1.5–5 months of treatment to achieve remission. The drug(s) were slowly withdrawn until complete cessation treatment. The total duration of immunosuppressive therapy varied between 3 and 22 months. These dogs remained in remission for the entire follow-up period (1.5–6 years after treatment).

A study performed at the University of Pennsylvania (USA) showed that dogs with EP had a longer life expectancy when antibiotics (usually cephalexin) were used in addition to immunosuppressants. It contradicts clinical supervision that dogs with EP do not develop concomitant pyoderma until they are started on immunosuppressive therapy. Moreover, another recent study found no difference in survival when antibiotics were used in initial therapy.

In a University of Pennsylvania study, survival was approximately 40%, with 92% of deaths occurring in the first year. In the same results, 10% of cases ended in long-term remission after drug withdrawal. In other researchers, long-term remission was achieved in about 70%.

Cats have a better prognosis for this disease than dogs. In the same University of Pennsylvania results, only 4 out of 44 cats died (from disease or treatment) during the entire study period. According to the author's experience, the annual survival rate exceeds 90%. In addition, a significant number of cats do not relapse after discontinuation of all medications.

Treatment

Treatment of any autoimmune skin disease requires frequent monitoring and vigilance for complications associated with immunosuppressive therapy, such as demodicosis, dermatophytosis, and bacterial pyoderma. Interestingly, the author has rarely seen a dog with EP present with secondary pyoderma on first examination. It develops much more often after the start of immunosuppressive therapy. If the patient was under control and relapsed, or the patient you are trying to get into remission gets worse, there are two possible reasons. The first is an exacerbation of EP (with an increase / decrease in elements), and the second - secondary infection due to immune suppression. If new elements are located in the follicles, three folliculotropic infections should be excluded - bacterial, demodicosis and dermatophytosis. The minimum examination that should be carried out when such elements appear: skin scrapings, Wood's lamp examination (screening) and impression smears. Whether or not to do fungal culture at this moment depends on how often you encounter dermatophytosis in your practice, and on the results of cytology (acantholytic keratinocytes, cocci, demodex). If dermatophytosis is common in your practice, culture should be done. Otherwise, culture for fungi and a second skin biopsy are performed as a second step if there is no adequate response to treatment.

In addition to the treatments described below, symptomatic therapy should include medicated shampoo. Since EN is clinically indistinguishable from superficial bacterial folliculitis, the author prescribes cephalexin (10–15 mg/kg 2–3 q/d) until histological results are obtained, unless EN is suspected to be caused by cephalexin.

There is no “best” treatment that works for all cases of EN, so treatment must be individualized.

For this reason, it is extremely important to self-examine the dog or cat before any adjustment in therapy and to monitor the course of the disease in detail. When planning treatment, the severity of the condition should be assessed to ensure that treatment does not more harm than the disease itself.

There are regional differences in the degree of aggressiveness of EN treatment. Some of them are associated with a different gene pool. Since EP worsens under the influence of sunlight, they may also be related to differences in duration daylight hours. In any case, avoiding sunlight is part of the treatment for EN.

Because diet is known to be a cause of (endemic) EN in humans, in the event of a poor response to initial therapy the author studies the dietary history and corrects the diet. In humans, thiols (garlic, onion), isothiocyanates (mustard, horseradish), phenols ( nutritional supplements) and tannins (tea, bananas, apples). Vitamin E (400-800 IU 2 times a day) and essential fatty acids can be added to the treatment volume due to their anti-inflammatory and antioxidant properties.

The basis for the treatment of autoimmune skin diseases are glucocorticosteroids (GCS). They can be applied both locally and systemically, depending on the severity of the disease and the area of ​​the lesion. Because some cats cannot metabolize inactive prednisone to active form, prednisolone, in cats, prednisone alone should be used. In dogs, both can be used. The author observed cases of EP in cats that were well controlled on prednisolone, but relapsed on prednisone and returned to remission only after re-prescribing prednisone - all at exactly the same dosage.

The most powerful veterinary local preparation is a synotic containing fluocinolone acetonide. If the disease is localized, the author prescribes the drug 2 times a day. until clinical remission is achieved (but not more than 21 days), and then slowly cancels over several months. Make sure the owner wears gloves when applying this medication.

Dogs with more severe disease are given prednisone or prednisolone 1 mg/kg bid. for 4 days, and then by mg / kg 2 r. / d. for the next 10 days. Re-examinations are carried out every 14 days. If remission is achieved, the dose is reduced by 25% every 14 days. The author defines remission as the absence of active (fresh) elements (no pustules, and any crusts are easily removed, and the underlying epidermis looks pink and without erosion). You can not reduce the dose too quickly! The goal is to keep the dog on 0.25 mg/kg or less every other day. If this is not achievable, azathioprine is added to therapy (see below).

Some dermatologists use combination therapy from the outset, but in the author's experience, at least 75% of dogs can be maintained exclusively on corticosteroids, with additional risks and costs associated with the use of azathioprine. Only in the absence of a response to corticosteroids or in case of insufficient use every other day should azathioprine be added to the treatment.

For the treatment of cats, only prednisolone is used. In fact, only prednisolone can be found in the author's first aid kit - in order to avoid inadvertently giving prednisone to a cat. Dose for cats 1 mg/kg 2 times a day. within 14 days. The prednisolone regimen for cats is then similar to that for dogs. If it is not possible to control the disease on prednisolone, chlorambucil (not azathioprine!) is added to therapy.

If the animal does not respond to prednisolone, other immunosuppressive agents must be added (see below).

Animals receiving GCS for a long time, regardless of the dose, require monitoring of general and biochemical blood tests, general analysis urine and urine culture (to rule out asymptomatic bacteriuria) every 6 months.

Azathioprine is an antimetabolite, a competitive purine inhibitor. Purine is essential for normal synthesis DNA, therefore, in the presence of azathioprine, defective DNA is synthesized, which prevents cell division. The action of azathioprine reaches full potency with a delay of 4-6 weeks. The drug is prescribed simultaneously with GCS. Initial dose of azathioprine 1.0 mg/kg 1 r./d.

After achieving remission and canceling or reducing GCS to minimum doses, azathioprine intake is tapered every 60-90 days. The author usually reduces not the dose, but the frequency of administration, first appointing every other day, and then 1 time in 72 hours. Complete (with platelet count) and biochemical blood tests are monitored every 14 days for 2 months, then every 30 days for 2 months, then every 3 months as long as the dog is on azathioprine. Possible side effects include anemia, leukopenia, thrombocytopenia, hypersensitivity reactions (especially in the liver), and pancreatitis. Azathioprine should not be given to cats as it can cause irreversible bone marrow depression.

Chlorambucil is indicated for cats and dogs that do not respond to or cannot tolerate azathioprine. The treatment regimen/precautions/monitoring for chlorambucil is the same as for azathioprine. Initial dose 0.1-0.2 mg/kg/day.

The combination of tetracycline and niacinamide has many anti-inflammatory and immunomodulatory properties and is therefore often used to treat various immune-mediated skin diseases such as DLE, vesicular cutaneous lupus erythematosus (idiopathic ulcerative lesion collie and sheltie skin), lupus onychodystrophy, erythematous pemphigus, metatarsal fistula of German shepherds, aseptic panniculitis, aseptic granulomatous dermatitis (idiopathic aseptic granuloma-pyogranuloma syndrome), vasculitis, dermatomyositis and cutaneous histiocytosis. The author uses this combination for all these diseases, if they are relatively mild. If any of these diseases do not respond to immunosuppressive therapy, dogs can be treated with this combination. The dosage of tetracycline and niacinamide for dogs less than 10 kg - 250 mg of both every 8 hours, for dogs heavier than 10 kg - 500 mg of both every 8 hours. With a clinical response (which usually takes several months), the drugs are slowly withdrawn - first up to 2, and then up to 1 r / day. Side effects are rare, and when they occur, they are usually caused by niacinamide. These include vomiting, anorexia, drowsiness, diarrhea, and increased liver enzymes. Tetracycline may lower the seizure threshold in dogs. In cats, it is preferable to use doxycycline at a dose of 5 mg/kg 1-2 times a day. Doxycycline in cats should be given either liquid form, or in tablets, but be sure to give 5 ml of water after that. The use of doxycycline can lead to esophageal strictures in cats!

If the above treatment fails in dogs, cyclosporine A, a calcineurin inhibitor, is given orally at a dose of 5 mg/kg bid. Isolated cases of successful treatment of EP in cats (especially the claw form) are also described. Recently there was a message about the effectiveness local application tacrolimus in the treatment of facial epilepsy and pemphigus erythematosus. Experience with the use of this drug by the author is insufficient.

A specific approach may be applied to mild cases of facial EN (or pemphigus erythematosus): topical corticosteroids and/or tetracycline-niacinamide. With generalized forms or with severe course facial / plantar forms, prednisolone should be used according to the scheme described above. While remission is established at each examination, the dose of prednisolone is gradually reduced, as described above. If at the control examination after 14 days remission is not achieved or it is not stable at the dose of hormones<0,25 мг/кг каждые 48 часов, тогда в лечение добавляются азатиоприн (у собак) или хлорамбуцил (у кошек).

If the disease does not respond to treatment, make sure the diagnosis is correct (make sure that dermatophytosis, demodicosis and bacterial pyoderma are excluded).

If the diagnosis is confirmed, try switching to dexamethasone or triamcinolone. The initial dose is 0.05-0.1 mg/kg 2 times a day, and then reduced in the same way.

As a last resort in refractory cases of EN, pulsed corticosteroid therapy at high doses is successful. After pulse therapy, prednisolone is continued at a dose of mg/kg 2 times a day. with a gradual decrease.

There are two pulse therapy protocols:

1. 11 mg/kg of methylprednisolone sodium succinate (per 250 ml of 5% glucose) i.v. 1 p./d. 3-5 days;
2. 11 mg/kg prednisone po bid 3 days.

Discoid lupus erythematosus (DLE)

The approach to diagnosing DLE is the same as for EP, taking into account the dog's individual characteristics, history, physical examination, histological examination, and response to treatment. In dogs, DKV is the second most common autoimmune skin disease. The author has never seen it in cats. According to the literature, there is no association of the disease with age, but according to the author's experience, it is more common among young and adult dogs. Some dermatologists list Collies, Shelties, German Shepherds, Siberian Huskies, and Breton Spaniels as high-risk breeds.

Clinical manifestations include depigmentation, erythema, erosions, crusting, and alopecia. When the nose is involved, it loses its cobblestone texture and becomes bluish-gray. DLE usually begins on the nose and may extend to the bridge of the nose. In addition, the lips, periorbital zone, auricles and genitals can be affected. The well-being of dogs does not suffer.

DLE should be differentiated from mucocutaneous pyoderma, pemphigus, skin reaction to drugs, erythema multiforme, cutaneous lymphoma, Vogt-Koyanagi-Harada syndrome (neurodermatouveitis), systemic scleroderma, solar dermatitis, and fungal infections.

Mucocutaneous pyoderma (the author adheres to the term "antibiotic sensitive dermatitis" because bacteria are not detected on histology) is a disease that affects the lips, nose, bridge of the nose, periorbital zone, genitals and anus. Clinically, it is indistinguishable from DKV. There is no identifiable cause for this disease, so the diagnosis is based on the characteristics of the dog (adult, most often a German Shepherd or its cross), the clinical presentation (type and distribution of elements) and, most importantly, response to antibiotic therapy. In the past, it was differentiated from DLE by histological findings. DLE was then defined by lichenoid lymphocytic or lymphocytic plasma cell superficial dermatitis with hydropic degeneration and/or isolated necrotic keratinocytes involving the basal cell layer. There was pigment incontinence and basement membrane thickening. Mucocutaneous pyoderma was determined by lichenoid plasma cell or lymphocytic plasma cell infiltration without surface changes and damage to the basal cell layer. However, these criteria have been called into question after a recent study, the results of which showed that DLE and mucocutaneous pyoderma can be histologically indistinguishable! In this study, dogs were divided on the basis of histological findings into three groups: with lymphocytic lichenoid superficial dermatitis with hydropic degeneration, with plasma cell lichenoid dermatitis, and mixed with lymphocytic plasma cell lichenoid superficial dermatitis with hydropic degeneration. The authors then determined how different groups responded to treatment with antibiotics or immunomodulators. There was no statistical difference in histological features between groups II and III! The author now takes the view that in all cases of nasal dermatitis in dogs, a 30-day course of cephalexin should be given before immunomodulatory therapy. In fact, a 3-4 week course of cephalosporins before a biopsy is justified and often makes it possible to establish a diagnosis without a biopsy!

The best approach to nasal dermatitis that is clinically similar to "typical" DLE is to understand that it is more of a reaction pattern than a disease. This pattern (lymphocytic plasma cell lichenoid dermatitis of the nasal region) may respond to antibiotics or require immunomodulatory therapy. Since the results of the biopsy are identical, it would be correct to prescribe a 30-day trial course of cephalosporin before the biopsy.

Diagnostics

Dogs with DLE are clinically healthy. Hematological or serological changes are not noted (including a negative analysis for ANA). Historically, lymphocytic or lymphocytic plasma cell lichenoid superficial dermatitis with hydropic degeneration of basal keratinocytes has been considered the characteristic histological changes in DLE. Scattered apoptotic keratinocytes may be present.

Treatment

When treating dogs with DLE, it is important to understand that this is primarily a cosmetic condition. Sometimes dogs are bothered by itching. In this light, it is important to treat each case according to the severity of the symptoms. You must be sure that the treatment will do no more harm than the disease itself. The author treats DKV in stages, each new appointment being added to the previous one, unless otherwise indicated. Initially, cephalexin 10-15 mg/kg 2 times a day is prescribed. within 30 days (given that DKV and mucocutaneous pyoderma are indistinguishable). If the dog does not respond to cephalexin, it is stopped and the following are given: avoidance of sunlight, UV protection, vitamin E and omega-3 fatty acids. Niacinamide and tetracycline are prescribed according to the scheme described above. If after 60 days the dog does not respond to treatment, the next step is to assign local corticosteroids (starting with moderately strong). If there is no response after 60 days, tetracycline and niacinamide are withdrawn and systemic prednisolone (anti-inflammatory doses) is given, which is then slowly withdrawn over several months until the lowest possible dose is reached.

Bibliography

1. Scott DW, Miller WH, Griffin CE. Muller & Kirk's Small Animal Dermatology. 6th ed. Philadelphia: WB Saunders; 2001:667-779.
2. Willemse T. Auto-immune dermatoses. In: Guaguere E, Prelaud P, eds. A Practical Guide to Feline Dermatology. Merial. 1999: 13.1-13.7.
3. Marsella R. Canine pemphigus complex: Pathogenesis and clinical presentation. Comp on Cont Ed for the Pract Vet. 22(6):568-572, 2000.
4. Rosenkrantz W.S. Pemphigus foliaceus. In: Griffin CE, Kwochka KW, MacDonald JM, eds. Current Veterinary Dermatology. St. Louis: Mosby-Year Book. 1993: 141-148
5. Olivry T. Canine pemphigus folicaeus: an update on pathogenesis and therapy In: Clinical Program Proceedings of the Fifth World Congress 222-227
6. Gomez SM, Morris DO, Rosenbaum MR, et.al. Outcome and complications associated with the treatment of pemphigus foliaceus in dogs: 43 cases (1994-2000). JAVMA 2004;224(8):1312-16.
7. Olivry T., et al. Prolonged remission after immunosuppressive therapy in 6 dogs with pemphigus foliaceus. Vet Dermatol 2004;15(4):245.
8. Rosenkrantz W.S. Pemphigus: Current Therapy. Vet Dermatol 2004:15:90-98
9. Mueller RS, Krebs I, Power HT, et.al. Pemphigus Foliaceus in 91 Dogs J Am Anim Hosp Assoc 2006 42:189-96
10. White SD, Rosychuk RAW, Reinke SI, et al. Tetracycline and niacinamide for treatment of autoimmune skin disease in 31 dogs. J Am Vet Med Assoc 1992; 200:1497-1500.
11. Nguyen, Vu Thuong, et al. Pemphigus Vulgaris Acantholysis Ameliorated by Cho-linergic Agonists" Archives of Dermatology 140.3 (2004): 327-34.
12. Chaffins ML, Collison D, Fivenson DP. Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: a review of 13 cases. J Am Acad Dermatol. 1993;28:998-1000.

Prepared according to the materials: "PROCEEDINGS OF THE MOSCOW INTERNATIONAL VETERINARY CONGRESS, 2012

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 exposure of the animal 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 hypothalamus-pituitary-adrenal cortex relationship, 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 in 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 dog cases 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 back 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, tampons moistened with Miramistin solution were used to treat the areas of skin damaged by pustules, 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.

Bibliography:

1.Medvedev K.S. Diseases of the skin of dogs and cats. Kyiv: "VIMA", 1999. - 152 p.: ill.

2. Paterson S. Skin diseases of dogs. Per. from English. E. Osipova M.: "AQUARIUM LTD", 2000 - 176 p., ill.

3. Paterson S. Skin diseases of cats. Per. from English. E. Osipova M.: "AQUARIUM LTD", 2002 - 168 p., ill.

4. Roit A., Brostoff J., Mail D. Immunology. Per. from English. M.: Mir, 2000. - 592 p.

5 Bloom P.B. Diagnosis and treatment of autoimmune skin diseases in dogs and cats. [Electronic resource] - Access mode. - URL: http://webmvc.com/show/show.php?sec=23&art=16 (accessed 04/05/2015).

6.Dr. Peter Hill BVSc PhD DVD DipACVD DipECVD MRCVS MACVSc Veterinary Specialist Centre, North Ryde - Pemphigus foliaceus: review of clinical signs & diagnosis in dogs and cats [electronic article].

7. Jasmin P. Clinical Handbook of Canine Dermatology, 3d ed. VIRBAC S.A., 2011. - p. 175.

8.Ihrke P.J., Thelma Lee Gross, Walder E.J. Skin Diseases of the Dog and Cat 2nd ed. Blackwell Science Ltd, 2005 - p. 932.

9. Nuttall T., Harvey R.G., McKeever P.J. A Color Handbook of Skin Diseases of the Dog and Cat, 2nd ed. Manson Publishing Ltd, 2009 - p. 337.

10 Rhodes K.H. The 5-minute veterinary consult clinical companion: small animal dermatology. USA: Lippincott Williams & Wilkins, 2004 - p. 711.

11. Scott D.W., Miller W.H., Griffin C.E. Muller & Kirk's Small Animal Dermatology. 6th ed. Philadelphia: WB Saunders; 2001:667-779.