Autoimmune diseases. Autoimmune skin diseases in cats and dogs using the example of pemphigus foliaceus. causes, clinical signs, diagnosis, treatment

J-L. PELLERIN, C. FOURNELE, L. CHABAN

Autoimmune hemolytic anemia (AHA) is the most commonly identified type of autoimmune disease in dogs and cats (Person J.M., Almosni R, Quintincolonna F, Boulouvis H.J., 1988). In dogs, primary AGA occurs due to an autoimmune disease. Severe secondary AGA of a non-traumatic nature is often detected (Squires R., 1993).

AGA is one of the most characteristic classical examples of autoimmune diseases. Consequently, autoantibodies are involved in the pathogenesis of AGA (Miller G., Firth F.W., Swisher S.N., Young L.E., 1957). In humans, the specificity of target antigens has been identified: there are autoantibodies for the blood group antigen (Person J.M. et al., 1988).

AGA in humans was first discovered in 1945 using an anti-globulin test called the Coombs method. Miller G. et al. (1957) first reported AGA in the dog.

AGA has also been identified in mice, guinea pigs, horses (Miller G. et al., 1957; Taylor F.G.R., Cooke B.J., 1990), cattle (Dixon P.M. etal. 1978; FengerC.K., et al. ., 1992), sheep, pigs, dogs and cats (Halliwel R.E.W., 1982).

DEFINITION

The term “anemia” refers to a decrease in the concentration of hemoglobin in the circulating blood below 12 g per 100 ml in dogs and below 8 g per 100 ml in cats, which is accompanied by a decrease in oxygen transport.

AGA is defined as acquired severe hemolysis associated

Table 1. Classification of AGA (DMC = direct Coombs method),

ny with the presence of immunoglobulins on the surface of erythrocytes and sometimes in the blood serum, the action of which is directed towards the antigenic determinants of the patient’s erythrocyte membrane (Appendix 1).

AGA is characterized by two main criteria:

1. diagnosed using a blood test;

2. Autoantibodies are detected using the direct Coombs method.

Among hemolytic anemias of an immune nature, a distinction is made between secondary anemias that develop after allogeneic immunization, as a result of an infectious process or drug sensitization, as well as AGA itself, sensu stricto (in the strict sense of the word). Alloimmunization is very rare in dogs and cats.

CLASSIFICATION

AGA is classified according to immunological and clinical characteristics

Criteria

The clinical picture, laboratory results, pathogenesis, prognosis and treatment of AGA largely depend on the type of immunopathological process.

The immunological classification of AGA is based on the class of antibodies (IgG or IgM) and their functions - agglutinating or sometimes hemolytic.

The AGA classification includes five main classes (Table 1). Cold agglutinins are defined as agglutinating antibodies detected at a temperature of +4°C. They always belong to the IgM class.

Impact on prognosis and therapy

AGA occurs most often in dogs and is caused by the action of autoimmune IgG, both together with complement and separately (Cotter S.M., 1992).

1. If IgG is expressed on the surface of erythrocytes in association with complement or without its participation (class I and III), then this disease is mainly of an idiopathic nature with an acute and transient course. The clinical picture of the disease is characterized by the consistent development of hemolysis, sometimes severe and with remissions. This primary IgG-associated AGA responds well to treatment with corticosteroids and is usually not associated with secondary AGA due to any underlying medical conditions. According to Klag etcol. (1993), among 42 dogs tested, 74% were positive for IgG and negative for complement. Such AGAs are mainly classified as class III.

2. If we are talking about IgM antibodies (classes II, IV and V), then the disease is less amenable to corticosteroid therapy and is more often of a secondary nature (oncological, infectious)

Table 2. Diseases of dogs and cats associated with AGA (according to Werner L).

* Diseases caused by peri- or intraerythrocytic agents may be responsible for the development of immune-mediated hemolytic anemia without the involvement of autoantibodies, which may occur secondarily and be complicated by the development of true AGA.

infectious or any other autoimmune disease). Such AGAs can be detected directly or indirectly through the presence of C3b and IgM during elution or washout.

The prognosis of AGA associated with C3b and IgM is more questionable compared to IgG.

Common immunological disorders

In one and the same patient it is often necessary to observe a large number of different antibodies in combination.

tania with anti-erythrocyte autoantibodies. Canine AGA is especially often combined with systemic lupus erythematosus (SLE) or autoimmune thrombocytopenia. In the latter case we are talking about Evans syndrome.

Evans syndrome (E. Robert, American, 1951)[English. Evans "syndrome]. This is de Ficher-Evans syndrome. Association of an autoimmune disease with thrombocytopenic purpura. Rarely found in humans, has a questionable prognosis.

AGA is sometimes observed in association with autoimmune dermatosis, characterized by the presence of IgG and complement depots at the level of the dermoepidermal junction (Hasegawa T. et al., 1990). Antierythrocyte autoantibodies are a factor in extensive immunological disorder even in the absence of a clinical picture of the disease.

Clinical classification

The immunological classification must conflict with the strict clinical one, as it contrasts idiopathic AGA with secondary AGA. Autoimmune hemolytic anemia, characterized by the presence of warm antibodies (IgG), corresponds to “idiopathic”, while AGA associated with the persistence of cold antibodies (IgM) is “secondary”.

Idiopathic AGA

With primary or so-called idiopic AGA, no concomitant diseases are noted. In dogs, the frequency of AGA of idiopathic nature is 60-75% of cases. In cats, this disease is rare, since secondary AGA predominates in them due to an infectious disease caused by the leukemia virus (FeLV) (Jackon M.L et al., 1969).

Secondary AGA

In 25-40% of cases in dogs and in 50-75% of cases in cats, AGA is associated with other diseases. AGA precedes, accompanies or follows another disease, sometimes occurring without any specific clinical symptoms (Table 2). The prognosis and effectiveness of treatment depends on the underlying cause of AGA.

Secondary AGA in cats is mainly associated with FeLV infection or haemobartonella felis.

The frequency of detection of IgM on erythrocytes in cats significantly exceeds IgG, while in dogs IgG autoantibodies predominate. The higher content of IgM antibodies in cats compared to dogs explains the predominance of the autoagglutination reaction.

CLINICAL PICTURE SYMPTOMS OF THE DISEASE AND LABORATORY RESEARCH RESULTS

In humans, a high positive correlation has been identified between the signs of clinical, hematological, and immunological manifestations of AGA (Stevart A.F., Feldman B.F., 1993).

Clinical symptoms

AGAs appear at any age, but are most often observed from 2 to 7 years. The time of year also influences (Klag A.R., 1992), since 40% of AGA cases are detected in May and June. In humans, an increase in the incidence of AGA disease was also found in the spring (Stevart A. F., Feldman B. F., 1993).

Gender and breed are not factors predisposing to this disease.

The onset of the disease may be progressive or sudden. AGA is characterized by a combination of five pathognomonic symptoms:

1) loss of strength, lethargy (86%)

2) pallor of mucous membranes (76%)

3) hyperthermia

4) tachypnea (70%)

5) tachycardia (33%).

The three main reasons for visiting a veterinarian are: brown urine, anorexia (90%) and loss of strength (Desnoyers M., 1992). Hepatomegaly and splenomegaly are not always detected (25% of cases); a similar trend is noted for lymphadenopathy (Stewart A.R., Feldman B.F., 1993).

Prostration and sometimes lethargy are also observed. Little or no jaundice (50% of cases).

Petechiae and ecchymosis (bruising) are observed only in cases where thrombocytopenia occurs. According to Klag A.R. et al. (1993) moderate or severe thrombocytopenia was observed in 28 of 42 dogs (67%).

The intensity of anemia can vary and depends on 2 factors:

1) degree of hemolysis,

2) compensatory ability of the bone marrow.

The intensity of anemia in primary AGA is more pronounced than in secondary AGA.

Quite rarely, when cold agglutinins (IgM) are detected, more often with idiopathic AGA, anemia is generally moderate, with isolated episodes of intensification.

Cyanosis and necrosis of the end parts of the body (ears, fingers, tail, nose), capable of evolving into gangrene, sometimes with a fatal outcome, are the most pathognomonic signs of this disease (Vandenbusshe P. etal., 1991).

Drawing. 1. Coombs method: agglutination reaction.

Table 3. Norms for general biochemical analysis in domestic carnivores (according to Crespeau).

Appendix 3.

All these injuries in dogs and cats are associated with circulatory disorders caused by agglutination of red blood cells in the peripheral capillaries, where the body temperature is significantly lower than that of its visceral part.

Clinical blood test

In the presence of AGA, the red blood cell count falls below 5,000,000/ml. Hematocrit is greatly reduced (up to 8-10%), a similar picture is observed for hemoglobin (up to 4 g/100 ml). Normocytic, normochromic and sometimes macrocytic anemia is noted (Jones D.R.E. et al., 1992, 1991, 1990).

The presence of small colored spherocytes is noteworthy (photo 1), and neutrophilia is sometimes noted (Desnoyers M., 1992).

Sometimes we observe phagocytosis of erythrocytes by monocytes. AGA in dogs most often has a regenerative form (Appendix 2). The total number of reticulocytes varies from 20 to 60%. In 30% of dogs, mild reticulocytosis is noted (1-3% reticulocytes), in 60% it is moderate or severe (more than 3% reticulocytes). Poorly regenerative and nonregenerative AGA have been described in dogs (Jonas L.D., 1987). Currently, these forms of the disease are being detected more and more often.

Blood chemistry

All dogs have severe bilirubinuria (brown urine) with urobilinuria, as well as hyperbilirubinemia (not conjugated). Jaundice is present in approximately 50% of cases. Increased hemoglobinemia is sometimes accompanied by hemoglobinuria, but the symptom of intravascular hemolysis does not appear so often (10% of 42 dogs) (Klag A.R. etal., 1993). At the same time, there is a noticeable decrease in haptoglobin and serum iron, while uricemia (uric acid in the blood) increases in 50% of cases. As the disease develops, the indicators vary, sometimes the changes are long-lasting or interrupted with subsequent relapses.

METHODS OF IMMUNOLOGICAL DIAGNOSTICS

Direct Coombs test

This method is a priority in diagnosing AGA (Person et al., 1980).

Principle

The Coombs test is an immunological method that determines the presence of non-agglutinating antibodies due to the action of xenogeneic (from another species) anti-immunoglobulin serum, which provokes agglutination. Using the direct Coombs test alone, a diagnosis of this disease is made. In clinical practice, this method is used for humans, dogs and cats.

The principle of operation of the direct Coombs test, or the so-called special species antiglobulin test, is based on the effect of sensitization of red blood cells with the help of immunoglobulin or complement fixed on their membrane, or due to both together (Stewart A.R, 1993).

The mechanism of the proposed method is to create bridges between antibodies that coat the surface of red blood cells using species-specific “anti-antibodies” or specific antiglobulins (Fig. 1).

At the first stage, polyvalent antiglobulins are used, directed against all serum globulins.

Table 4. Interpretation of the results of the direct Coombs method (according to Cotter).

Classification

The following reagents have been developed for humans: anti-IgG, anti-IgM, anti-lgA and anti-SZ.

For dogs, in routine diagnosis, one polyvalent antiglobulin is used, sometimes three antiglobulins: one polyvalent and two specific - anti-IgG and anti-SZ (Jones D.R.E., 1990).

Using specific reagents, it has been established that most often erythrocytes are sensitized by IgG alone (AGA type IgG), or IgG in combination with complement (AGA mixed type), in particular with C3d expressed (present) on the erythrocyte membrane.

Sometimes the cause of erythrocyte sensitization is complement alone (complement type AGA). This type of anemia is due solely to the action of IgM, since IgM in the Coombs test usually elutes spontaneously during the washing process. In this case, after washing at 37°C, only C3d remains on the surface of erythrocytes.

IgM can be detected through anticomplement using the Coombs method, or using the same method, but carried out in the cold, in which elution of IgM does not occur during the washing process. In this case, we are talking about Cold IgM agglutinins, when spontaneous agglutination can be observed in dogs at +4°C.

Antibodies of the IgA class are extremely rare.

Each antiglobulin has species-specific properties. Staging the Coombs reaction with feline red blood cells means the need for timely preparation or acquisition of an antiglobulin reagent for this type of animal. Kits designed to perform this test on humans or dogs are not suitable for cats.

In domestic carnivores, AGA detected with cold antibodies are much less common than with warm antibodies.

Execution technique

Blood for analysis (Appendix 3) must be taken with an anticoagulant (citrate or EDTA - ethylenediaminetetraacetic acid). It is essential that the medium in the test tube contains a calcium chelating agent. In a blood sample, it provokes nonspecific fixation of complement on red blood cells in vitro and leads to a false positive reaction. This is why heparin is not used as an anticoagulant.

After thorough washing (three or five times centrifugation from 5 minutes at 800d to 5 minutes at 1500d), the test sample of the suspension is ADJUSTED to a 2% concentration. It is recommended to carry out the direct Coombs reaction as soon as possible from the moment the material is taken, preferably within 2 hours. The blood sample should be stored at 37°C. After incubation for one hour at 37°C with different serial dilutions of the three antisera, the sample is kept at room temperature (1-1.5 hours). The reaction results are taken into account visually in the wells of microplates placed on a Kahn mirror, or using a microscope (x100).

In parallel, it is necessary to carry out negative controls:

1. A 2% suspension of the patient’s erythrocytes in the presence of an isotonic NaCl solution in order to test the ability of the tested erythrocytes to spontaneous agglutination in the absence of antiglobulins. According to Desnoyers M. (1992), autoagglutinins are responsible for spontaneous autoagglutination both at 37°C (class I) and at 4°C (class IV). In cats, autoagglutination of erythrocytes is common (Shabre V., 1990). Diluting the blood in an equivalent volume of isotonic NaCl solution eliminates this artifact due to the dissociation of tube-shaped red blood cells, without having a negative effect on real autoagglutinins (Squire R., 1993).

2. Mixing a 2% suspension of erythrocytes from a healthy dog ​​(control animal) with species-specific serum antiglobulin allows you to check the quality of the antiserum.

If clinical symptoms suggest IgM-mediated AGA, the clinician may request a routine Coombs test at 37°C as well as a cold Coombs test at 4°C to detect cold-active antibodies (types IV and V) (Vandenbussche P. , et al., 1991).

This test is not suitable for cats. The fact is that many normal cats have non-agglutinating antibodies that become active at lower temperatures and are detected using the direct Coombs test at 4°C. In this species of animals, the method of indirect hemagglutination at 4°C should be used.

Discussion

Laboratory diagnosis of AGA is almost entirely based on the direct Coombs method in combination with a general blood test. Interpretation of a positive reaction in the Coombs test is not difficult.

If the detected antibodies belong to the IgG class, then it is very likely that the detected anemia is of autoimmune origin.

The significance of identifying a positive result in the Coombs test of the “IgG + complement” type in mixed type AGA requires discussion, since there is no complete confidence that complement is fixed on the complex formed by IgG with erythrocyte membrane antigens.

It turned out that it is even more difficult to establish the reliability of erythrocyte sensitization in AGA, detected using a positive Coombs test in a reaction to “pure complement”.

It is possible that some of the Coombs complement tests correspond to the temporary fixation of antigen-antibody complexes that quickly elute from the surface of erythrocytes.

AHA is differentiated from true hyperhemolysis by the following characteristics: increased reticulocytosis, unconjugated hyperbilirubinemia, etc. Sometimes the Coombs test gives a false-positive or false-negative result (Table 4). This is quite rare (about 2% of cases), but a negative reaction to the Coombs test can occur with true AGA, especially if the number of fixed immunoglobulins is insufficient (less than 500 per red blood cell).

The clinical symptoms of AGA are in many ways similar to piroplasmosis, which is very common in France. This requires the clinician to systematically carry out the Coombs test in the case of hemolytic anemia in the absence of a positive response to classical treatment, when the animal has piroplasmosis, even if the persistence of piroplasmosis in the blood is established, because this disease can simultaneously be accompanied by AGA.

Elution

If using the Coombs method it is possible to determine which class sensitized antibodies belong to, then elution allows one to determine their specificity. Elution at high temperature with ether or acid allows a pool of antibodies to be collected and tested on a panel of red blood cells of the appropriate species using the indirect Coombs method (Person J.M., 1988).

Table 5. Doses of cytotoxic immunosuppressive drugs used and possible toxic effects.

This is mainly done in human medicine, where panels with typed red blood cells are available.

In animals, acid elution is of particular importance when a false-positive reaction of specific antibodies to an antigen artificially fixed on the surface of red blood cells is suspected. If the eluate obtained from the erythrocytes of a dog suspected of having the disease does not give an agglutination reaction with a pool of erythrocytes obtained from dogs with different blood groups, then we are talking about AGA (Tsuchida et al., 1991).

Indirect Coombs method

Its principle is to detect the presence of free autoantibodies in the blood serum against red blood cells.

The blood of a sick dog should be collected in a clean, dry tube and centrifuged. The test serum is incubated in the presence of red blood cells, washed three times and obtained from a healthy dog ​​of the same blood type as the sick animal. The level of free autoantibodies in the serum is often very low because all antibodies present are tightly bound to the surface of the red blood cells. In 40% of cases, the amount of free antibodies is insufficient to obtain a positive reaction in the indirect Coombs method (Stevart A.R, 1993).

MECHANISMS OF erythrocyte destruction

AGA is part of a group of autoimmune diseases for which the role of autoantibodies in pathogenesis has been clearly and convincingly demonstrated.

It is the binding of autoantibodies to specific antigens on the erythrocyte membrane that is responsible for reducing their lifespan, which is mediated by three cytotoxic mechanisms: 1) phagocytosis; 2) direct hemolysis with the participation of complement; 3) antibody-dependent cellular cytotoxicity.

Extravascular erythrophagocytosis

In most cases, phagocytosis of erythrocytes by macrophages is observed. Red blood cells sensitized by autoantibodies are destroyed after opsonization by macrophages of the spleen, liver, and, to a lesser extent, bone marrow. Bilirubinemia, as well as the presence of urobilin and bilirubin in the urine, prompt the clinician that extravascular hemolysis is occurring (Chabre V., 1990).

Minor differences in pathogenesis are present between the two red blood cell graveyards.

Extravascular erythrophagocytosis can be combined with intravascular hemolysis.

Complement-mediated intravascular hemolysis

Destruction of red blood cells in the circulation system is a rather rare phenomenon (in 15% of dogs), which is observed exclusively in acute hemolytic anemia, or in acute complications that develop during the chronic course of the disease (classes II and V).

This is explained by the complete activation of complement along the classical pathway from C to SD on the surface of the same erythrocytes. As a result, the membrane of red blood cells is destroyed and their components (mainly hemoglobin) are released into the circulating blood, which leads to hemoglobinemia and hemoglobinuria.

This is observed only when autoantibodies to complement are fixed with a pronounced hemolytic effect: the role in hemolysis is now clearly established for IgG and IgM. Only these forms of autoimmune disease can be accompanied by icterus or subicterus.

Antibody-induced cell cytotoxicity

K-cells (killer cells or killer cells) have receptors for the Fc fragment of the IgG molecule, with which they are fixed on the surface of sensitized erythrocytes and cause their death through direct cytotoxic effects.

The role of this third mechanism in the development of AGA has recently been clearly established, but not yet fully defined.

As with other autoimmune diseases, the degree of autoimmune disorders is not always directly proportional to the severity of the manifestation of the process.

Short term forecast

The short-term prognosis is unfavorable only in 15-35% of cases. Clinical improvement after adequate therapy is observed, according to various authors, in 65-85% of patients.

An increase in hematocrit and reticulocytosis against the background of a decrease in spherocytosis are positive prognostic criteria.

Dog mortality increases significantly under the following circumstances: poor regeneration (moderate or insufficient reticulocytosis), low hematocrit (below 15%), blood bilirubin concentration above 100 mg/l.

Long term forecast

The long-term prognosis is less favorable in terms of possible complications. Usually you have to be content with the fact that recovery is achieved only in 30-50% of cases.

The prognosis for secondary AGA depends mainly on the concomitant disease and its possible complications.

Most often, pulmonary thromboembolism and disseminated intravascular coagulation are observed (Cotter S.M., 1992). In rare cases, complications such as lymphadenitis, endocarditis, hepatitis or glomerulonephritis are noted, which can lead to death (Stewart A.F., Feldman B.F., 1993).

For class III disease, the prognosis is most often favorable. In cats, the prognosis is guarded, since the disease is often associated with infection caused by one or another retrovirus (feline leukemia virus, FeLV; feline immunodeficiency virus, VIF) (ChabreB., 1990).

A more cautious prognosis for diseases of classes II and V, accompanied by intravascular hemolysis.

The prognosis is questionable for diseases belonging to classes I and IV and accompanied by autoagglutination (Hagedorn J.E., 1988). They are more likely than others to end in death.

According to Klag et col. (1992, 1993) the overall mortality rate is about 29%.

In any case, the prognosis should always be restrained and depend on the adequacy of pharmacological correction of the condition.

Therapy for AGA can be carried out in various ways. The most common treatment approach is based on eliminating the immunological reaction by prescribing immunosuppressants that suppress the formation of autoantibodies and the activity of macrophages responsible for erythrophagocytosis.

Immunosuppressants

Corticosteroids are the main component of therapy. They are used both as monotherapy and in association with danazol, cyclophosphamide or azathioprine (Cotter S.M., 1992; Squires R., 1993).

Corticosteroids

At high therapeutic doses and with long-term use, corticosteroids are the main drugs that provide the effect of immunosuppression. From the clinician's point of view, prednisone (Cortancyl N.D. per os), prednisolone, methylprednisolone (methylprednisolone hemisuccinate: Solumedrol N.D., i.v.), prescribed in loading doses of 2 to 4 mg/kg every 12 hours, give the best result. You can also use dexamethasone or betamethasone in doses of 0.3-0.9 mg/kg per day (Stewart A.F., Feldman B.F., 1993).

If corticosteroid therapy is effective in AGA with warm autoantibodies (IgG) in 80-90% of cases, then in AGA with cold autoantibodies (IgM) its effectiveness is ambiguous. However, the data obtained should be assessed carefully. If corticosteroid therapy is ineffective, it is necessary to resort to cytotoxic chemotherapy.

Impact corticosteroid therapy should be started as soon as possible after confirmation of the diagnosis of AGA using the direct Coombs method. Treatment should not be long: the duration varies on average from three to eight weeks. A longer course of corticosteroid therapy has little benefit but carries a risk of severe complications (iatrogenic Cushing's syndrome).

For maintenance therapy, corticosteroids are prescribed every other day in doses equal to half, a quarter or one-eighth of the shock dose. Gradual withdrawal of drugs is carried out within two to four months after clinical remission. For some animals, corticosteroids are stopped completely. Others continue to be treated at low doses throughout their lives to prevent relapses (Squires R., 1993).

In dogs with idiopathic AGA (IgG), the Coombs test remains positive throughout the course of the disease, including during corticosteroid therapy and clinical remission. When the reaction is negative in the direct Coombs method, relapse of the disease is quite rare. This is a very favorable prognostic criterion (Slappendel R.J., 1979).

In cats, corticosteroid therapy is combined with the prescription of tetracycline antibiotics if hematological examination reveals hemobartenellosis (Haemobartenella felis), or for the prevention of bacterial complications against the background of immunosuppression.

Corticosteroid therapy should not be administered long-term in cats, especially for FeLV infection. The immunosuppressive effects of corticosteroids may enhance the already pronounced immunosuppressive effect of the virus. In cats with latent viral infection, corticosteroid therapy may exacerbate the pathology and cause viremia.

If in the first 48-72 hours after the start of corticosteroid therapy it is not possible to achieve stabilization or improvement in hematocrit, then therapy should be continued. A noticeable increase in hematocrit may occur 3-9 days after the start of therapy. If there is no improvement after 9 days, then more powerful immunosuppressive drugs should be used.

Powerful immunosuppressants

Cyclophosphamide and azathioprine are two cytotoxic drugs (cytostatics) that are more potent immunosuppressants than corticosteroids (Table 5). They suppress the production of antibodies by B lymphocytes (Squires R., 1993).

These drugs should be used only in the most severe cases of AGA disease: patients with autoagglutination (classes I and IV) or with intravascular hemolysis (classes II and V) (Hagedorn J.E., 1988). In severe cases, vigorous therapeutic measures are required. It is imperative to inform animal owners about the side effects of medications.

Cyclosporine (10 mg/kg, IM, then orally for 10 days) has been successfully used to treat complex recurrent cases of AGA that do not respond to classical corticosteroid therapy (Jenkins TS. et al., 1986; Preloud P., Daffos L, 1989 ). Patients with autoagglutination (classes I and IV) require combination therapy (corticosteroids + cytostatics) to prevent relapses and achieve remission. However, larger trials are required to better understand how effective this combination is in the treatment of AGA.

Danazol

Danazol (ethisterone derivative), a synthetic androgen hormone, is increasingly used to treat autoimmune diseases (Stewart A.F., 1945). Danazol reduces the production of IgG, as well as the amount of IgG and complement fixed on cells (Holloway S.A. etal., 1990).

The main mechanism of action of danazol is to inhibit the activation of complement and suppress the fixation of complement on cell membranes (Bloom J.C., 1989). Danazol modulates the ratio of T-helper and T-suppressor cells, which is disturbed in autoimmune thrombocytopenia (Bloom J.C., 1989). It can also reduce the number of receptors for the Fc fragment of immunoglobulins located on the surface of macrophages (Schreiber A.D., 1987).

The therapeutic dose for dogs is 5 mg/kg, 3 times a day orally (Stewart A.R., Feldman B.F., 1993). The effect of danazol (Danocrine N.D., Danatrol M.D.) increases slowly over one or three weeks and is manifested in an improvement in hematological parameters (Bloom J.C., 1989; Schreiber A.D., 1987). It is recommended to combine danazol with any corticosteroid (Stewart A.F., Feldman B.F., 1993). When the patient's condition has stabilized, the dose of corticosteroids is reduced, and treatment with danazol is continued for two to three months (Schreiber A.D., 1987). Danazol can cause a noticeable increase in muscle mass if used for more than six months.

Splenectomy

The purpose of splenectomy is to remove the spleen, which is the main organ of red blood cell destruction in IgG-related AGA. It is also the main organ of the lymphoid system that produces circulating antibodies, in this particular case autoantibodies. Successfully used in humane medicine, this operation probably cannot be as beneficial for dogs and cats (Feldman B.F. et al., 1985). It is completely useless in IgM-related AGA, where destruction of red blood cells mainly occurs in the liver. Moreover, performing this operation may cause an exacerbation of the latent course of babesiosis or hemobartonellosis. Thus, we propose to consider splenectomy only as a last resort (Feldman B. Fetal., 1985).

Blood transfusion

Blood transfusion is generally contraindicated due to the possibility of hemolysis. Transfused red blood cells quickly become covered with autoantibodies, which leads to their massive rupture and, consequently, aggravation of the hemolysis crisis. On the other hand, blood transfusion reduces normal bone marrow hematopoiesis. Therefore, it should be prescribed for the following indications: hemolytic crisis, hematocrit below 10% or respiratory failure.

In practice, the indication for blood transfusion is considered to be a drop in the red blood cell count below 2x106/ml in dogs and 1.5x106/ml in cats. Very short-term improvement is noted with intravenous corticosteroids. Plasmapheresis gives positive results in humans, but in animals its use is complicated by the low availability of equipment for dogs and cats (Matus R.E. etal., 1985).

Adjuvant therapy

As with all anemia, adjuvant therapy is used: ferrous sulfate at the rate of 60-300 mg per day (Squires R., 1993), vitamin B12, a quiet environment, heat, and then intravenous infusion, sometimes forced breathing. It is especially important that patients with cold agglutinins are protected from exposure to extremely cold temperatures. Prevention of thromboembolism and DIC syndrome in dogs at risk (increased levels of total bilirubin, condition after blood transfusion) consists of early administration of anticoagulants: 100 U/kg heparin subcutaneously every 6 hours during the exacerbation period (Klein M.K. et al., 1989).

Patient monitoring

This makes a big difference. Monitoring the condition of patients can be carried out using the Coombs test: two months from the moment the patient enters the acute phase of the disease, then every 2-3 months upon transition to the chronic course. If the clinical and hematological assessment criteria indicate normality, the Coombs test gives a negative reaction, the dog or cat can be considered recovered. However, it is difficult to talk about true recovery or simple remission.

In this case, you should be extremely careful, since with a probability of 50% any of the above options is possible.

To clarify the true situation, it is necessary to continue monitoring the animal’s condition, systematically conduct blood tests (for example, once a month for six months, and then once every three months) and, at the slightest threat of relapse, resume corticosteroid therapy. As a rule, this is enough to normalize the clinical condition. A minimal dose of corticosteroids (0.05-1 mg/kg per day) every other day helps restore blood counts to physiological norms. In case of chronic or recurrent course of AGA, permanent administration of corticosteroids is recommended whenever possible in the minimum therapeutic dose.

CONCLUSION

When the clinical picture is sufficiently indicative, then using only one direct Coombs method, a diagnosis of AGA can be made. But this applies only to a positive Coombs test reaction in the presence of IgG (both with and without complement). In general, positive reactions with complement alone are common in dogs and are rarely associated with significant hemolysis. If a preliminary diagnosis is made, then additional research is necessary. As with all autoimmune diseases, nonspecific disorders in the immune system can be caused by a variety of reasons.

And finally, all autoimmune diseases have similarities, with each representing a group of disorders that, to varying degrees, overlap each other. Often, simultaneous or sequential manifestations of AGA and systemic lupus erythematosus, and AGA and rheumatoid polyarthritis, or AGA and autoimmune thrombocytopenia can be observed. If an immunological diagnosis reveals the presence of one of these autoimmune diseases, then it is imperative to look for others, even in the absence of characteristic clinical symptoms. When AGA is associated with SLE or thrombocytopenia in a dog, or with FeLV infection in a cat, the prognosis is more questionable compared with isolated idiopathic AGA.

magazine "Veterinarian" No. 2003

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

Diagnosis of any skin disease is based on a thorough history, 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 not collected correctly.

Pemphigus (pemphigus)

In pemphigus, the immune system mistakenly attacks desmosomes. Desmosomes are point-to-cell contacts that connect, in particular, keratinocytes.

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

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

When collecting an anamnesis, the owner may report that the elements wax and wane, that the development of the disease was slow (especially in cases with localization exclusively on the muzzle) or that the elements appeared acutely (most often with a generalized lesion). During generalization, dogs often have a fever, swelling of the limbs and general signs are observed. Itching in any form may be absent or may be moderate.

There are three patterns of primary spread of ES:

1. facial form (the most common), which affects the bridge of the nose, nose, periorbital area, ears (especially in cats);
2. plantar form (only paronychia can be observed in cats);
3. a generalized form in which elements appear on the face and then spread (note - in dogs, elements sometimes appear throughout the body at once).

The elements go through the following stages of development: erythematous spot pustule annular ridge (“collar”) erosion yellow-brown crust. Due to the involvement of hair follicles, multifocal or diffuse alopecia is often observed.

The primary element of EP is large pustules not associated with follicles (pustules in follicles are also present), most often on the bridge of the nose, paw pads, nose and ears (in cats, elements can be localized around the nipples). In comparison, pustules in bacterial pyoderma are localized to the follicles, located on the abdomen and/or torso, 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 by systemic damage, distal limb edema, fever, drowsiness, and lymphadenopathy.

The differential includes any disease accompanied by pustules, crusts and desquamation, for example, erythematous pemphigus, zinc deficiency dermatosis (especially involving the footpads), metabolic epidermal necrosis (especially involving the footpads), bacterial and fungal (dermatophytosis) infections, demodicosis , discoid lupus erythematosus (DLE) (facial/nasal form), erythema multiforme, mycosis, leishmaniasis and inflammation of the sebaceous glands.

Diagnostics

A cytological preparation of the pustule or crust must be made. Microscopy will show acantholytic keratinocytes, either individually or in clusters, surrounded by intact neutrophils and/or eosinophils in the absence of bacteria. The only method confirming pemphigus is histology. A biopsy should be taken from the intact pustule or, if it is absent, from the crust. Proteases from bacteria (in pyoderma) or dermatophytes (Trichophyton mentagrophytes) destroy intercellular glycoproteins (desmoglein), leading to acantholysis. Because these infectious diseases are very similar to EP histologically, special stains for both bacteria (Gram) and fungi (GMS, PAS) should be used when making the diagnosis from biopsy. The author routinely performs a culture for dermatophytes in all cases of suspected EP.

Forecast

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

Drug-induced EP occurs when a drug stimulates the body's genetic predisposition to develop EP. Typically, this form of EN should be treated like idiopathic EN. There is currently no way to determine whether drug-associated EN is drug-induced or drug-provoked. 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 EP 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 out of 51 dogs with EP were able to go into long-term remission without medication. Interestingly, these dogs were from areas with high UV exposure (North Carolina or Sweden).

In this group of dogs, 1.5–5 months of treatment were required to achieve remission. The drug(s) were slowly withdrawn until treatment was completely discontinued. The total duration of immunosuppressive therapy varied between 3 and 22 months. These dogs remained in remission throughout the subsequent observation period (1.5-6 years after treatment).

A study carried out at the University of Pennsylvania (USA) showed that the life expectancy of dogs with EP was longer when antibiotics (usually cephalexin) were used in addition to immunosuppressants. This is in contrast to the clinical observation that dogs with EP do not develop concomitant pyoderma until they are started on immunosuppressive drugs. Moreover, another recent study found no difference in survival when antibiotics were used as initial therapy.

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

Cats have a better prognosis for this disease than dogs. In the same results from the University of Pennsylvania, only 4 of 44 cats died (from the disease or from treatment) during the entire study period. In the author's experience, the annual survival rate exceeds 90%. In addition, a significant number of cats do not experience relapses after stopping 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 initial examination. It develops much more often after the start of immunosuppressive therapy. If a patient has been in care and relapses, or the patient you are trying to get into remission deteriorates, there are two possible causes. The first is an exacerbation of EP (with an increase/decrease of elements), and the second is a secondary infection due to suppression of the immune system. 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, examination in a Wood's lamp (screening) and fingerprint smears. Whether or not to culture for fungi at this point depends on how often you encounter dermatophytosis in your practice, and on the results of cytology (acantholytic keratinocytes, cocci, demodex). If dermatophytosis occurs frequently in your practice, a culture should be done. Otherwise, fungal culture and repeat skin biopsy are performed in the second stage if there is no adequate response to treatment.

In addition to the treatments described below, medicated shampoo should be included in symptomatic therapy. Since EP is clinically indistinguishable from superficial bacterial folliculitis, the author prescribes cephalexin (10-15 mg/kg 2-3 times a day) before obtaining histology results, except in cases where there is a suspicion that EP is provoked by cephalexin.

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

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

There are regional differences in the degree of aggressiveness of EN treatment. Some of them are associated with different gene pools. Because EC is impaired by sunlight, it may also be related to differences in daylight hours. In any case, avoiding sunlight is part of the treatment for EP.

Since it is known that diet can be a cause of EP (endemic) in humans, in the case of a poor response to initial therapy, the author reviews the nutritional history and makes dietary adjustments. In humans, thiols (garlic, onion), isothiocyanates (mustard, horseradish), phenols (food additives) and tannins (tea, bananas, apples) have been described as the cause of endemic PE. 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 used both locally and systemically, depending on the severity of the disease and the area affected. Because some cats cannot metabolize inactive prednisone into the active form, prednisone, only prednisone should be used in cats. Both can be used in dogs. The author has observed cases of EP in cats that were well controlled on prednisone, but relapsed on prednisone and returned to remission only after re-administration of prednisone - all at exactly the same dosage.

The most powerful veterinary local drug is 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 withdrawn over several months. Make sure the owner wears gloves when applying this medication.

Dogs with more severe disease are prescribed prednisone or prednisolone at a dose of 1 mg/kg twice a day. for 4 days, and then mg/kg 2 times a day. for the next 10 days. Repeated 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 appears pink and without erosion). Do 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 possible, 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 solely on corticosteroids, with the added risks and costs associated with azathioprine. Only in the absence of a response to GCS or in case of insufficient use every other day should azathioprine be added to the treatment.

Only prednisolone is used to treat cats. In fact, only prednisolone can be found in the author's medicine cabinet - to avoid inadvertently giving prednisone to the cat. Dose for cats 1 mg/kg twice a day. within 14 days. The prednisolone regimen for cats then follows that for dogs. If the disease cannot be controlled with prednisone, chlorambucil (not azathioprine!) is added to therapy.

If the animal does not respond to prednisolone, other immunosuppressants 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 urinalysis and urine culture (to exclude asymptomatic bacteriuria) every 6 months.

Azathioprine is an antimetabolite, a purine competitive inhibitor. Purine is necessary for normal DNA synthesis, so in the presence of azathioprine, defective DNA is synthesized, which prevents cell division. The effect of azathioprine reaches its full effect with a delay of 4-6 weeks. The drug is prescribed simultaneously with GCS. The initial dose of azathioprine is 1.0 mg/kg once a day.

After achieving remission and discontinuing or reducing corticosteroids to minimal doses, azathioprine intake is reduced every 60-90 days. The author usually reduces not the dose, but the frequency of administration, initially prescribing every other day, and then once every 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 for the entire period while 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 may cause irreversible bone marrow suppression.

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. The initial dose is 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 of the skin of collies and shelties), 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 may be able to add this combination to their treatment. The dosage of tetracycline and niacinamide for dogs less than 10 kg is 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 to 2, and then to 1 dose per day. Side effects are rare, and when they occur, they are usually caused by niacinamide. These include vomiting, anorexia, drowsiness, diarrhea, and elevated 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 should be given to cats either in liquid or tablet form, but be sure to give 5 ml of water afterwards. The use of doxycycline can lead to esophageal strictures in cats!

If the above treatment fails in dogs, cyclosporine A, a calcineurin inhibitor, is used orally at a dose of 5 mg/kg 1 time per day. Isolated cases of successful treatment of EP in cats (especially the claw form) have also been described. Recently, there was a report on the effectiveness of topical tacrolimus in the treatment of facial EP and erythematous pemphigus. The author has insufficient experience using this drug.

A specific approach can be applied to non-severe cases of facial EP (or erythematous pemphigus): topical corticosteroids and/or tetracycline-niacinamide. For generalized forms or for severe facial/plantar forms, prednisolone should be used according to the scheme described above. While remission is determined at each examination, the dose of prednisolone is gradually reduced as described above. If, at a follow-up examination after 14 days, remission is not achieved or it is not stable with 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 that 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 according to the same scheme.

As a last chance for refractory cases of EP, pulse therapy with high doses of corticosteroids can be 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 methylprednisolone sodium succinate (per 250 ml of 5% glucose) IV 1 time per day. 3-5 days;
2. 11 mg/kg prednisone orally once a day. 3 days.

Discoid lupus erythematosus (DLE)

The approach to diagnosing DLE is the same as for EP - taking into account the individual characteristics of the dog, medical history, physical examination, histological examination and response to treatment. In dogs, DLE is the second most common autoimmune skin disease. The author has never encountered it in cats. According to the literature, there is no connection between the disease and age, but in the author’s experience, it is more common among young and adult dogs. Some dermatologists consider collies, shelties, German shepherds, Siberian huskies and Breton Epagnoles to be 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 at the tip of the nose and may spread to the bridge of the nose. In addition, the lips, periorbital area, ears and genitals may be affected. The dogs' well-being 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”, since bacteria are not detected on histology) is a disease that affects the lips, nose, bridge of the nose, periorbital area, genitals and anus. Clinically, it is indistinguishable from DLE. There is no identifiable cause for this disease, so diagnosis is based on the characteristics of the dog (adult, most often a German Shepherd or cross), clinical presentation (type and distribution of elements) and, most importantly, response to antibiotic therapy. In the past, it was differentiated from DLE based on histology. 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 thickening of the basement membrane. Mucocutaneous pyoderma was determined by lichenoid plasma cell or lymphocyte plasma cell infiltration without surface changes or damage to the basal cell layer. However, these criteria have been called into question by a recent study showing that DLE and mucocutaneous pyoderma may be histologically indistinguishable! In this study, dogs were divided based on histology into three groups: lymphocytic lichenoid superficial dermatitis with hydropic degeneration, plasma cell lichenoid dermatitis, and a mixed group 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 were no statistical differences in histological features between groups II and III! The author is now of the view that all cases of nasal dermatitis in dogs should be treated with a 30-day course of cephalexin 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 recognize that it is a response pattern rather 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 performing it.

Diagnostics

Dogs with DLE are clinically healthy. There are no hematological or serological changes noted (including a negative ANA test). Historically, the characteristic histological changes in DLE have been considered to be lymphocytic or lymphocytic-plasma cell lichenoid superficial dermatitis with hydropic degeneration of basal keratinocytes. Scattered apoptotic keratinocytes may be present.

Treatment

When treating dogs with DLE, it is important to understand that it 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 DLE in stages, each new prescription being added to the previous one, unless otherwise indicated. Initially, cephalexin 10-15 mg/kg twice a day is prescribed. within 30 days (given that DLE and mucocutaneous pyoderma are indistinguishable). If the dog does not respond to cephalexin, it is stopped and the following is prescribed: avoidance of sunlight, UV protective products, vitamin E and omega-3 fatty acids. Niacinamide and tetracycline are prescribed according to the regimen described above. If after 60 days the dog does not respond to treatment, the next step is to prescribe local corticosteroids (starting with moderately strong ones). If there is no response after 60 days, tetracycline and niacinamide are discontinued and systemic prednisolone (anti-inflammatory doses) is started, which is then tapered slowly over several months until the lowest possible dose is achieved.

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 Practitioner Vet. 22(6):568-572, 2000.
4. Rosenkrantz WS. 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 WS. 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 Cholinergic 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 based on materials: “PROCEDINGS OF THE MOSCOW INTERNATIONAL VETERINARY CONGRESS, 2012.”

What diseases do you think are still considered the most poorly studied and mysterious? Cancer or maybe HIV infection? This is partly true. But autoimmune pathologies are much more surprising. They also occur in domestic animals. One of the most unpleasant diseases of this type is pemphigus in cats.

Pemphigus is the general name for a group of autoimmune skin diseases that involve the formation of ulcers and crusts on the skin of an animal. In addition, these pathologies are characterized by the formation of multiple pustules and papules. The latter are quite decent in size, resembling multiple bubbles. Actually, the disease “owes” its name to this factor.

In some cases, pemphigus affects the gum tissue. Because it is an autoimmune disease, it is characterized by the presence of autoantibodies: antibodies produced by the immune system but that act against healthy body tissue. Simply put, white blood cells begin to kill the body. Accordingly, the severity of the course may depend on many factors.

The main pathological process manifested in this disease is called acantholysis. Without going into details, this is a phenomenon in which the connection between epidermal cells is lost. Instead of normal skin, a kind of “scale” appears. There are three types of pemphigus that affect cats: leaf-shaped, erythematous and ordinary (vulgaris).

The first type is the most severe, as it affects even the deepest layers of the skin. Erythematous is similar to the first type, but is easier. Oddly enough, ordinary pemphigus in some cases is even more severe than foliaceous pemphigus, since this pathology also affects the deep layers of the skin.

Read also: Cholangitis - inflammation of the bile ducts in cats

Predisposing factors

What causes the disease and what are its causes? Alas, we can’t talk about this with confidence, since they have been studied extremely poorly. In general, as is the case with any other autoimmune pathology.

In many cases, we have to admit that all types of disease have an idiopathic etiology. Simply put, the disease appears on one “wonderful” day, and nothing precedes its appearance at all. An assumption may immediately arise that the real reason is lost somewhere in the jungle of genetics and heredity. In addition, there is evidence that the development of the disease is promoted by excessive insolation (UV irradiation from the sun).

Clinical signs

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

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

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

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

• In severe cases, the gums are also involved in the process, resulting in problems with teeth (even tooth loss).

• Similarly, the nail beds are involved in the process, the animal’s claws begin to wobble and sometimes fall out. The process is very painful and causes great suffering to the animal.

• Swollen lymph nodes; when palpated, the cat clearly shows signs of displeasure. The animal becomes apathetic, with increasing fever and lameness (if claws are involved). Note that all these signs are characteristic only of a severe course of the process.

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

Read also: The cat is choking, wheezing and coughing: causes, treatment methods

How are other forms of pemphigus different? As for the erythematous variety, in many ways it is completely similar to the leaf-shaped one. But still, the symptoms of pemphigus in cats in this case are slightly different. First, lesions are usually limited to the head, muzzle and claw plates (more precisely, their bases). Secondly, with erythematous pemphigus, the lips are very often affected, which practically does not happen with other forms of this disease.

But what about “vulgar” pemphigus, that is, ordinary? It is characterized by the same symptoms as with the leaf-shaped form of the disease, only in some cases “multiplied” by a factor of two:

• The oral cavity is almost always affected, and the effects are very serious, including deep, non-healing ulcers on the mucous membrane of the inner surface of the cheeks and tongue. Because of this, cats with common pemphigus almost always lose their appetite and quickly lose weight.

• The axillary and groin areas, where the skin is thinnest and most delicate, are also captured. Accordingly, all this is very painful and itchy.

• Anorexia, depression, fever.

• Since the body with this type of pemphigus is greatly weakened, in most cases secondary bacterial infections develop.

Diagnostics and therapy

The diagnosis is not easy to make. This is done based on a combination of clinical signs, as well as on the basis of the results of a general and biochemical blood test. But the latter method often does not give any obvious result at all, since with pemphigus the blood test results are often completely normal. However, if the cat looks like a bubbling monster with an inflamed and pimply skin, but its blood is normal, this already gives reason to think about the autoimmune origin of the disease. So the tests are not useless.

Autoimmune disease – this is a disruption of the immune system, in which an attack begins on the organs and tissues of one’s own body. In other words, the immune system perceives its tissues as foreign elements and begins to damage them.

The immune system is a protective network consisting of white blood cells, antibodies and other components involved in fighting infection and rejecting foreign proteins. This system distinguishes “self” cells from “foreign” cells by markers located on the surface of each cell. This is why the body rejects transplanted skin flaps, organs and blood transfusions. The immune system can malfunction due to either an inability to do its job or an overactive job.

In autoimmune diseases, the immune system loses the ability to recognize “its own” markers, so it begins to attack and reject tissues of its own body as foreign.

The mechanism of autoimmune processes is similar to the mechanism of immediate and delayed types of allergies and boils down to the formation of autoantibodies, immune complexes and sensitized killer T lymphocytes.

The essence of autoimmune processes is that under the influence of pathogens of infectious and invasive diseases, chemicals, drugs, burns, ionizing radiation, and feed toxins, the antigenic structure of the 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-lymphocyte killers capable of carrying out aggression against altered and normal organs, causing damage to the liver, kidneys, heart, brain, joints and other organs.

Autoimmune diseases are organ (encephalomyelitis, thyroiditis, diseases of the digestive system caused by chronic intoxication and metabolic disorders) and systemic (autoimmune connective tissue diseases, rheumatoid arthritis). Can be primary or secondary. Primary ones arise as a result of congenital and acquired disorders in the immune system, accompanied by loss of tolerance of immunocompetent cells to their own antigens and the appearance of forbidden clones of lymphocytes.

A characteristic sign of autoimmune diseases is a long wave-like course.

The diagnosis of autoimmune diseases is made on the basis of anamnestic data . Clinical manifestations of the disease, hematological, biochemical and special immunological studies for the detection of antigens, antibodies, antigen+antibody complexes and sensitized lymphocytes.

Autoimmune eye diseases in animals:

• or Chronic superficial vascular keratitis is a lesion of the limbus and cornea of ​​the eye, resulting from a local chronic inflammatory process. The infiltrate formed under the corneal epithelium is replaced by scar tissue, which leads to a significant decrease in vision. The immune system considers one's own cornea to be foreign tissue and tries to reject it.

The first reports of pannus appeared in areas with increased ultraviolet activity (in Austria and the US state of Colorado). Today, the disease is registered in all countries of the world. And it’s no secret that cases of pannus in areas with increased ultraviolet activity are more severe and less treatable. This allows us to conclude that ultraviolet rays play an important role in the occurrence of this disease. This phenomenon is due to the fact that exposure to ultraviolet radiation on the cornea accelerates the rate of metabolic processes in the latter. And the more active the metabolic processes are, the more actively the immune system tries to reject it.

This pathology is most common in dogs of such breeds as German Shepherd, Black Terrier and Giant Schnauzer. It is much less common in dogs of other breeds.

• or Plasma lymphatic conjunctivitis of the third eyelid is a condition where a similar immune reaction affects the conjunctiva and third eyelid. Plasma is less likely to cause vision loss, but causes greater ocular discomfort.

This is an attack of the immune system against the organs and tissues of the body’s own, resulting in their structural and functional damage.
They can be primary, but more often secondary. More common are secondary autoimmune diseases associated with partial changes in self-antigens under the influence of toxins, drugs, microorganisms, parasites, denaturation of proteins of damaged cells, tissues and other factors, as well as immunization with antigens of microorganisms that have similar determinants with antigens of animal cells.
Etiology. Autoimmune diseases can arise as a result of congenital or acquired disorders in the immune system, accompanied by loss of tolerance of immunocompetent cells to their own antigens and the appearance of forbidden clones of lymphocytes. The development of autoimmune pathology is possible due to violations of the physiological isolation of autoantigens, to which there is no immunological tolerance: the lens of the eye, sperm, myelin, insoluble collagen, hidden determinants of proteins and cells. Often their development is associated with changes in their own antigens under the influence of toxins, drugs, viruses, proteolytic processing and denaturation of proteins of damaged cells and tissues. Many autoimmune lesions can arise from immunization with antigens common to both bacteria and body tissues. Thus, calves and piglets have similar antigenic determinants of the intestinal mucosa with E. coli O-antigens, and the intestinal and liver epithelium have similar antigens with Salmonella antigens. Various lesions of tissues and organs in animals also develop with the deposition of immune
antigen+antibody complexes.
In newborns, autoimmune diseases arise through the colostral route, when autoantibodies and lymphocytes sensitized against antigens of certain organs are transmitted to them through the colostrum of sick mothers. In cows and sows, autoimmune lesions of the digestive organs are often recorded, caused by profound metabolic disorders and feed intoxication. Therefore, among the diseases of this group in calves and piglets, dyspepsia (diarrhea) is most common.
autoimmune origin.
Pathogenesis. Primary autoimmune diseases are associated with disruption of immunological homeostasis and the release of autoantigens to which there is no immunological tolerance. Therefore, when the biological isolation barriers of these tissues are violated, their antigens come into contact with lymphocytes and an immune response develops. Secondary (acquired) autoimmune diseases can occur as a result of tissue damage and changes in their antigenic properties under the influence of exogenous and endogenous factors. An immune response develops to released intraorgan, intracellular and modified antigens with the formation of autoantibodies and sensitized lymphocytes, which cause damage to the corresponding organs. ^
Symptoms A characteristic feature of autoimmune diseases is a long wave-like course of the disease. In newborn animals, the disease develops after ingestion of colostrum containing autoantibodies and sensitized lymphocytes. In addition, patients exhibit clinical symptoms characteristic of damage to a specific organ or an entire organ system. Circulating autoantibodies and sensitized lymphocytes are found in the blood. During an exacerbation of the disease, autoantigens and antigen+antibody immune complexes can be identified. A positive reaction develops at the site of intradermal injection of antigens. ^
It should be noted that in immunopathology associated with profound disorders of protein, carbohydrate and fat metabolism, the most pronounced immune reactions are initially observed to antigens of the liver, pancreas and much weaker intestines, and in case of chronic feed intoxication - to the antigen of the mucous membrane of the stomach and small intestine and liver. Subsequently, these differences are smoothed out.
Pathological changes. In the affected organs, changes characteristic of immune inflammation are noted. In their parenchyma, dystrophic and atrophic changes and autoantibodies fixed on the cells are found, in the stroma - vascular disorders, exudation and infiltration by macrophages, lymphocytes, eosinophils and neutrophils. Among the cellular infiltrate, plasma cells containing autoantibodies are often found. Regional lymph nodes are in a state of hyperplasia with a pronounced plasmacytic reaction.
Diagnosis and differential diagnosis. The diagnosis of autoimmune diseases is made on the basis of anamnestic data, clinical manifestations of the disease, results of a pathological autopsy, hematological, biochemical and special immunological studies for the detection of antigens, antibodies, antigen+antibody complexes and sensitized lymphocytes.
The detection of autoantibodies and sensitized lymphocytes is of decisive importance in the intravital diagnosis of autoimmune diseases. To detect antibodies, immune diffusion reactions (IDR), indirect hemagglutination (IRHA), complement fixation (IF),
immunofluorescence (RIF), and sensitized lymphocytes internal
skin allergy test. Filtrates obtained from homogenates of organs of healthy animals are used as antigens. The presence of precipitation bands in RID, agglutination of erythrocytes at a dilution of 1:32 and higher in RNGA, delayed hemolysis of erythrocytes in a titer of 1:50 and higher in RSC, contour luminescence of cells in RID, an increase in the skin fold by 2 mm or more in response to the administered antigen during intradermal The test confirms an autoimmune disease.
The same reactions can also be used to detect antigens and immune complexes. However, they are more difficult to detect due to low concentrations in biological fluids.
When diagnosing autoimmune pathology, it is necessary to take into account that organ antigens in the blood, mammary gland secretions and urine are detected mainly in acute cases and exacerbations of the chronic process. Their appearance is combined with the development of alterative processes. Following the release of organ antigens, an immune response develops and autoantibodies and sensitized lymphocytes appear. As the processes fade, organ antigens first disappear from the blood and other biological fluids, then autoantibodies, immune complexes, and later sensitized lymphocytes.
Timely diagnosis of autoimmune pathology of the digestive organs in cows and sows by immunological changes in the blood and the development of delayed-type hypersensitivity makes it possible to predict the possibility of the emergence of autoimmune diseases of the digestive organs in newborn young animals, caused by the transmission of autoimmune factors through the colostral route.
Based on the identification of antigens, autoantibodies and immune complexes, autoimmune diseases of specific organs and systems are differentiated.
The forecast is cautious.
Treatment. In the complex treatment of sick animals with autoimmune pathology, anti-lymphocyte serum and anti-lymphocyte globulin are used intramuscularly in a dose of OD-0.2 mg/kg
cortisone, cortisone 0.5-1.0 Ib/kg and srolye
If the severity of the pathology and its complications develops, the necessary treatment is additionally prescribed. .„„--.- immunopathology reprevention. In the i!fush, the exchange, voschoot. and nutritional value has little damage - /.„„„„„„„osty in uterine livestock intoxications on In particular, autoimmune dyspepsia. In order to prevent it, and sensitized
origin**?ly of the muscular stomach of birds, lignin, poro.
loziva 2-3 times and be sure to add
new or whole blood healthy instructions. With mass non-
prescribe vitamin preparations GT) and after birth they feed well ^^therefore with immunoglobulins, serum
colostrum substitutes, iiiihash, _ yeomah and complexes
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reduction of autoimmune diseases. Scamming is not allowed
reasonable feeding and “R”ilated fungi containing diseased
pouring out low-quality boxes , P of toxic substances.
unreasonable treatment of patients, animals with pronounced alteratives, -
and inflammatory processes of various origins.