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

J-L. PELLERIN, C. FURNEL, L. SHABAN

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

AGA is one of the most characteristic classic examples of autoimmune diseases. Therefore, 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 a dog.

AGA has also been identified in mice, guinea pigs, horses (Miller G. et al., 1957; Taylor FG.R., Cooke B.J., 1990), cattle (Dixon P.M. et al. 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.

AHA is defined as acquired severe hemolysis associated with

Table 1. Classification of AGA (PMC = 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 with a blood test;

2. Autoantibodies are detected using the direct Coombs method.

Among hemolytic anemias of an immune nature, there are secondary anemias that develop after allogeneic immunization, due to 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 features.

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 +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 idiopathic in nature with an acute and transient course. The clinical picture of the disease is characterized by the gradual development of hemolysis, sometimes proceeding severely and with remissions. This IgG-associated primary AGA responds well to corticosteroid treatment and is generally not associated with secondary AGA due to any comorbidities. According to Klag etcol. (1993), among 42 dogs tested, 74% tested positive for IgG and negative for complement. Such AGAs are generally classified as class III.

2. If we are talking about IgM antibodies (classes II, IV and V), then the disease responds worse to corticosteroid therapy, often has a secondary nature (oncological, in-

Table 2 Diseases associated with SAGA in dogs and cats (according to Werner L).

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

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

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

Common immunological disorders

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

taniya with anti-erythrocyte autoantibodies. Canine AGA is especially common in association with systemic lupus erythematosus (SLE) or autoimmune thrombocytopenia. In the latter case, we are talking about Evans syndrome.

Evans Syndrome (E. Robert, Amer., 1951) [Eng. Evans "syndrome]. Si. syndrome de Ficher-Evans. Association of an autoimmune disease with thrombocytopenic purpura. Rarely occurs in humans, has a dubious prognosis.

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

Clinical classification

Immunological classification must be in conflict with strict clinical classification, 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) - "secondary".

Idiopathic AGA

In primary or so-called idiooptic AGA, no comorbidities are noted. In dogs, the incidence of idiopathic AGA is 60-75% of cases. In cats, this disease is rare, as they are dominated by secondary AGA 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 50-75% in cats, AGA is associated with other diseases. AGA precedes, accompanies or follows another disease, sometimes occurring without special 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 haemobartonellosis (Haemobartonella felis).

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

SYMPTOMS OF THE CLINICAL PICTURE OF THE DISEASE AND THE RESULTS OF THE LABORATORY STUDY

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

Clinical symptoms

AGA manifests itself at any age, but most often they are observed from 2 to 7 years. The season also affects (Klag A.R., 1992), since 40% of AGA cases are detected in May-June. In humans, an increase in the incidence of AGA in the spring was also found (StevartA.F, Feldman B.F., 1993).

Sex 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 energy (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. Jaundice, slight or absent (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.

Quite rarely, when cold agglutinins (IgM) are detected, more often in idiopathic AGA, anemia is generally moderately expressed, with separate episodes of intensification.

Cyanosis and necrosis of the terminal parts of the body (ears, fingers, tail, nose) that can evolve into gangrene, sometimes with a fatal outcome, are the most pathognomonic signs in this disease (Vandenbusshe P. et al., 1991).

Drawing. 1. Coombs method: agglutination reaction.

Table 3. Norms of 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 much lower than that of its visceral part.

Clinical blood test

In the presence of AGA, the number of erythrocytes falls below 5,000,000/ml. The hematocrit is greatly reduced (up to 8-10%), a similar picture is observed for hemoglobin (up to 4 g/100 ml). Note normocytic, normochromic and sometimes macrocytic anemia (Jones D.R.E. et al., 1992, 1991, 1990).

Attention is drawn to the presence of small colored spherocytes (photo 1), and sometimes neutrophilia is noted (Desnoyers M., 1992).

Sometimes we state phagocytosis of erythrocytes by monocytes. AGA in dogs is more often regenerative (Appendix 2). The total number of reticulocytes varies from 20 to 60%. In 30% of dogs, mild reticulocytosis (1-3% of reticulocytes) is noted, in 60% it is moderate or severe (more than 3% of reticulocytes). Weakly regenerative and regenerative 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 marked 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 intravascular hemolysis is less common (10% of 42 dogs) (Klag A.R. et al., 1993). At the same time, a decrease in haptoglobin and serum iron is noticeable, while uricemia (uric acid in the blood) increases in 50% of cases. With the development of the disease, the indicators vary, sometimes the changes are prolonged or interrupted with subsequent relapses.

METHODS OF IMMUNOLOGICAL DIAGNOSIS

Direct Coombs test

This method in the diagnosis of AGA is a priority (Person et al., 1980).

Principle

The Coombs test is an immunological method that detects the presence of non-agglutinating antibodies due to the action of xenogenic (from another species) anti-immunoglobulin serum that provokes agglutination. With the help of only one direct Coombs test, a diagnosis is made for this disease. 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 specific antiglobulin test, is based on the effect of sensitization of erythrocytes with the help of immunoglobulin or complement fixed on their membrane, or due to both of them together (Stewart A.R, 1993).

The mechanism of the proposed method is to use species-specific "anti-antibodies" or specific antiglobulins to create bridges between antibodies that cover the surface of erythrocytes (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-lgG, anti-IgM, anti-lgA, and anti-C3.

For dogs, one polyvalent antiglobulin is used in routine diagnostics, sometimes three antiglobulins: one polyvalent and two specific - anti-lgG and anti-C3 (Jones D.R.E., 1990).

With the help of specific reagents, it was found that most often erythrocytes are sensitized only by IgG alone (AHA of the IgG type), or IgG in combination with complement (AGA of a mixed type), in particular with C3d expressed (present) on the erythrocyte membrane.

Sometimes erythrocyte sensitization is caused by complement alone (AGA of the complement type). This type of anemia is associated exclusively with 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 the erythrocytes.

IgM can be detected through anticomplement using the Coombs method, or using the same method, but carried out in the cold, in which IgM is not eluted during washing. We are talking about IgM cold agglutinins, when at +4°C in dogs spontaneous agglutination can be observed.

IgA antibodies are extremely rare.

Each antiglobulin has species-specific properties. Setting up the Coombs reaction with feline erythrocytes means the need for timely preparation or purchase of an antiglobulin reagent for this type of animal. Kits designed for this test in 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 extremely important that the medium in the tube contains a calcium chelating agent. In a blood sample, it provokes non-specific fixation of complement on erythrocytes in vitro and leads to a false positive reaction. That is why heparin is not used as an anticoagulant.

After thorough washing (three or five centrifugations from 5 min at 800 g to 5 min at 1500 g), the test sample of the suspension is ADJUSTED to 2% concentration. Direct Coombs reaction is recommended to be carried out as soon as possible after taking the material, 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 three antisera, the sample is kept at room temperature (1-1.5 hours). The results of the reaction should be taken into account visually in the wells of microplates placed on the Cahn mirror, or using a microscope (x100).

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

1. 2% suspension of the patient's erythrocytes in the presence of isotonic NaCl solution to test the ability of the tested erythrocytes to spontaneously agglutinate 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, erythrocyte autoagglutination is common (Shabre B., 1990). Dilution of blood in an equivalent volume of isotonic NaCl solution eliminates this artifact due to the dissociation of tube-shaped erythrocytes, without adversely affecting true autoagglutinins (Squire R., 1993).

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

If clinical symptoms suggest IgM-mediated AGA, then the clinician may request a conventional 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 a direct Coombs test at 4 ° C. In this species, the method of indirect haemagglutination at 4°C should be used.

Discussion

The laboratory diagnosis of AGA is almost entirely based on the direct Coombs method in combination with a complete blood count. The 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 identified anemia is of autoimmune origin.

The significance of detecting a positive result in the IgG + complement Coombs test in mixed type AGA requires discussion, since there is no complete certainty 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 the formulation of a reaction to “pure complement”.

It is possible that part of the Coombs' complement tests correspond to the temporary fixation of antigen-antibody complexes, which are rapidly eluted from the surface of erythrocytes.

Differentiate AGA from true hyperhemolysis according to the following features: 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 erythrocyte).

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

Elution

If using the Coombs method it is possible to determine which class the sensitized antibodies belong to, then elution makes it possible to determine their specificity. Elution at high temperature with ether or acid allows you to collect a pool of antibodies and test them on a panel with erythrocytes of the appropriate type 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 there are panels with typed erythrocytes.

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 erythrocytes is suspected. If the eluate obtained from the erythrocytes of a dog suspected of having a 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 (Tsuchidae tal., 1991).

Indirect Coombs Method

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

The blood of a sick dog must be collected in a clean, dry test tube and centrifuged. The test serum is incubated in the presence of erythrocytes, washed three times and obtained from a healthy dog ​​of the same blood type as the sick animal. The level of free autoantibodies in serum is often very low, since all the antibodies present are tightly fixed on the surface of 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 belongs to the 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 the decrease in their life expectancy, 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. Erythrocytes 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 B., 1990).

Minor differences in pathogenesis are present between the two RBC graveyards.

Extravascular erythrophagocytosis may be associated with intravascular hemolysis.

Complement mediated intravascular hemolysis

Destruction of erythrocytes in the circulatory system is a rather rare phenomenon (in 15% of dogs), which is observed only in acute hemolytic anemia, or in acute complications that have developed during the chronic course of the disease (classes II and V).

This is due to the complete activation of complement along the classical path from C to CD on the surface of the same erythrocytes. As a result, the erythrocyte membrane is destroyed and their constituents (mainly hemoglobin) are released into the circulating blood, which leads to hemoglobinemia and hemoglobinuria.

This is observed only when fixing autoantibodies to complement with a pronounced hemolytic effect: the role in hemolysis is now well established for IgG and IgM. Only these forms of an autoimmune disease can be accompanied by ictericity or subictericity.

Cytotoxicity of cells caused by antibodies

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

Recently, the role of this third mechanism in the development of AGA has been well established, but not yet completely 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 different authors, in 65-85% of patients.

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

Mortality in dogs is significantly increased 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 of secondary AGA depends mainly on the underlying disease and its possible complications.

Most often, pulmonary thromboembolism and disseminated intravascular coagulation are observed (Cotter S.M., 1992). In rare cases, complications are noted in the form of lymphadenitis, endocarditis, hepatitis or glomerulonephritis, which can be fatal (Stewart A.F., Feldman B.F, 1993).

In class III disease, the prognosis is most often favorable. In cats, the prognosis is poor, 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 doubtful in diseases belonging to classes I and IV and accompanied by autoagglutination (Hagedorn J.E., 1988). They are more likely 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 the pharmacological correction of the condition.

AGA therapy can be administered in a variety of ways. The most common treatment approach is based on the elimination of 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

In 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.) given at loading doses of 2 to 4 mg/kg every 12 hours give the best result. You can also use dexamethasone or betamethasone at 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 evaluated very carefully. If corticosteroid therapy is ineffective, cytotoxic chemotherapy should be considered.

Shock corticosteroid therapy should be initiated as soon as possible after confirmation of the diagnosis of AGA by 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 is associated with a risk of severe complications (iatrogenic Cushing's syndrome).

With maintenance therapy, corticosteroids are prescribed every other day in doses equal to half, a quarter, or one-eighth of the shock. The gradual withdrawal of drugs is carried out within two to four months after clinical remission. Some animals are completely off corticosteroids. Others continue to be treated at low doses throughout life to avoid 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, the recurrence 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 administration of tetracycline antibiotics if hematological examination reveals hemobartenellosis (Haemobartenella felis), or to prevent bacterial complications against the background of immunosuppression.

Corticosteroid therapy should not be given long-term in cats, especially in FeLV infections. The immunosuppressive effect of corticosteroids may enhance the already pronounced immunosuppressive effect of the virus. In cats with a 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 marked increase in hematocrit may occur 3-9 days after initiation of therapy. If there is no improvement even 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: 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. Be sure to inform pet owners about the side effects of drugs.

Cyclosporine (10 mg/kg, IM, then orally for 10 days) has been successfully used to treat complex recurrent cases of AGA that are not amenable 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 AGA therapy.

Danazol

Danazol (an ethisterone derivative), a synthetic hormone of the androgen group, is increasingly being 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. et al., 1990).

The main mechanism of action of danazol is to inhibit complement activation and to suppress complement fixation on cell membranes (Bloom J.C., 1989). Danazol modulates the ratio of T-helpers and T-suppressors, 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 PO 3 times a day (Stewart A.R, Feldman B.F., 1993). The action of danazol (Danocrine N.D., Danatrol M.D.) increases slowly over one or three weeks and is manifested in the improvement of 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 stabilizes, the doses of corticosteroids are 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 the case of IgG-associated AGA. It is also the main organ of the lymphoid system producing circulating antibodies, in the particular case of autoantibodies. Successfully applied in humanitarian medicine, this operation probably cannot be so favorable for a dog and a cat (Feldman B.F. et al., 1985). It is completely useless in AGA associated with IgM, where the destruction of red blood cells mainly occurs in the liver. Moreover, this operation can exacerbate the latent course of babesiosis or hemobartonellosis. Thus, we propose to consider splenectomy only as an extreme option (Feldman V. Fetal., 1985).

Blood transfusion

Blood transfusion is generally contraindicated due to the possibility of hemolysis. Transfused erythrocytes are rapidly covered with autoantibodies, which leads to their mass 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 a drop in the number of red blood cells 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 instrumentation for cats (Matus R.E. et al., 1985).

adjuvant therapy

As with all anemias, adjuvant therapy is used: ferrous sulfate at the rate of 60-300 mg per day (Squires R., 1993), vitamin B12, calm environment, warmth, and then intravenous infusion, sometimes forced breathing. It is especially important that patients with cold agglutinins be protected from exposure to too low temperatures. Prevention of thromboembolism and DIC in dogs at risk (elevated total bilirubin, condition after hemotransfusion) consists in the early administration of anticoagulants: 100 U / kg of heparin s / c every 6 hours during the exacerbation period (Klein M.K. et al., 1989).

Patient follow-up

This is of great importance. Control over the condition of patients can be carried out using the Coombs test: two months after the patient enters the acute phase of the course of the disease, then every 2-3 months during the transition to the chronic course. If the criteria for clinical and hematological assessment are normal, the Coombs test gives a negative reaction, it can be considered that the dog or cat has 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 condition of the animal, 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. The minimum dose of corticosteroids (0.05-1 mg / kg per day) every other day helps to restore blood counts to the physiological norm. In chronic or recurrent AGA, permanent administration of corticosteroids, whenever possible, at the lowest therapeutic dose is recommended.

CONCLUSION

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

Finally, all autoimmune diseases share similarities, with each representing a group of disorders that overlap to varying degrees. Often, one can observe the simultaneous or sequential manifestation of AGA and systemic lupus erythematosus, and AGA and rheumatoid arthritis, or AGA and autoimmune thrombocytopenia. If an immunological diagnosis reveals the presence of one of these autoimmune diseases, then it is necessary 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 uncertain compared with isolated idiopathic AGA.

magazine "Veterinarian" № 2003

Paul B Bloom 1.2
1. Clinic of Allergology, 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 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)

In pemphigus, the immune system mistakenly attacks the 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 skin disease 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 indicates that Chow Chows and Akitas are at an increased risk of this disease. There was no relationship between incidence and sex.

Three forms of EP are described in the literature - spontaneous pemphigus, drug-associated (both caused and provoked by drugs) and a form associated with chronic skin disease, 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, edema of the limbs and general signs are observed. 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. Due to the involvement of hair follicles, multifocal or diffuse alopecia is often observed.

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 by systemic involvement, 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 involving the paw pads), metabolic epidermal necrosis (especially involving the paw pads), 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 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 are very similar to EP histologically, special staining 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 the body's genetic predisposition to develop EN. 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 areas with high UV exposure (North Carolina or Sweden).

In this group of dogs, it took 1.5–5 months of treatment to achieve remission. The drug(s) was slowly canceled until the complete cessation of 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. This is contrary to the clinical observation 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 if the patient you are trying to get into remission worsens, there are two possible causes. The first is an exacerbation of EP (with an increase / decrease in elements), and the second is a 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 point 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, a medicated shampoo should be included in symptomatic therapy. 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 available, 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 the treatment does 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 a different gene pool. Because EP worsens with exposure to sunlight, they may also be related to differences in daylight hours. In any case, avoiding sunlight is part of the treatment for EN.

Because diet is known to be a cause of (endemic) EP in humans, in the event of a poor response to initial therapy, the author reviews the dietary 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 EP. 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 the active form, prednisolone, prednisone alone should be used in cats. In dogs, both can be used. The author observed cases of EP in cats that were well controlled on prednisolone, but relapsed on prednisolone and returned to remission only after re-prescribing prednisolone - all at exactly the same dosage.

The most powerful veterinary topical 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 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 on glucocorticosteroids alone, 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 urinalysis and urine culture (to exclude asymptomatic bacteriuria) every 6 months.

Azathioprine is an antimetabolite, a competitive purine inhibitor. Purine is necessary for normal DNA synthesis, 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 stopping or reducing GCS to minimal doses, azathioprine intake is reduced 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. CBC and CBC are monitored every 14 days for 2 months, then every 30 days for 2 months, then every 3 months for 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 skin ulceration of collies and shelties), lupus onychodystrophy, pemphigus erythematosus, German shepherd metatarsal fistula, 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 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 in either 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 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, topical tacrolimus has been reported to be effective 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. In generalized forms or in severe cases of 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 the 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 characteristic of the 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

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

What do you think, what diseases are still considered the most poorly understood and mysterious to this day? Cancer or maybe HIV infection? Partly it is. But much more astonishment is caused by autoimmune pathologies. They are also found in pets. One of the most troublesome 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 an animal's skin. 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 is “owed” by 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 that act against healthy body tissues. 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 that manifests itself in this disease is called acantholysis. If you do not go into details, then this is a phenomenon in which the connection between the cells of the epidermis is lost. Instead of normal skin, a kind of "scale" appears. There are three types of pemphigus that affect cats: foliate, erythematous and common (vulgaris).

The first variety is the most difficult, since even the deepest layers of the skin are affected with it. Erythematous is similar to the first type, but is easier. Oddly enough, but ordinary pemphigus in some cases is even harder than leaf-shaped, since even with this pathology, the deep layers of the skin are affected.

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

Predisposing factors

What causes the disease and what are its causes? Alas, but it is not necessary to speak about this with certainty, since they have been studied extremely poorly. In general, as in the case of any other autoimmune pathology.

In many cases, it must be recognized that all types of disease have an idiopathic etiology. Simply put, the disease occurs on one "beautiful" day, and absolutely nothing precedes its appearance. It may immediately be assumed that the real cause is lost somewhere in the wilds of genetics and heredity. In addition, there is evidence that excessive insolation (UV radiation from the sun) contributes to the development of the disease.

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.

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

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

• Swollen 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 is possible due to seeding with pyogenic microflora of opened papules and ulcers.

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

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, the lesions are usually limited to the head, muzzle, and ungual plates (more precisely, their base). Secondly, with erythematous pemphigus, the lips are very often affected, which practically does not happen with other forms of this disease.

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

• The oral cavity is almost always affected, and the effects are very serious, up to 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 lose weight quickly.

• The axillary and inguinal regions are also captured, where the skin is the thinnest and most delicate. Accordingly, all this hurts and itches a lot.

• Anorexia, depression, fever.

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

Diagnostics and therapy

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

autoimmune disease - This is a violation of the activity of the immune system, in which an attack of the organs and tissues of one's own body begins. In other words, the immune system perceives its tissues as foreign elements and begins to damage them.

The immune system is a defense network 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. That is why the body rejects transplanted skin flaps, organs and transfused blood. The immune system can malfunction, either due to the inability to do its job, or its overactive performance.

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

The mechanism of autoimmune processes is similar to the mechanism of immediate and delayed types of allergy and is reduced to the formation of autoantibodies, immune complexes and sensitized T-lymphocytes-killers.

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

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

A characteristic feature of autoimmune diseases is a long undulating course.

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- this is a lesion of the limbus and the 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 its own cornea to be a foreign tissue and tries to reject it.

The first reports of pannus appeared in areas with high ultraviolet activity (in Austria and the US state of Colorado). To date, 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 difficult 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, the more actively the immune system tries to reject it.

This pathology is most common in dogs of breeds such 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 response affects the conjunctiva and the third eyelid. Plasmoma is less threatening to loss of vision, but delivers more ocular discomfort.

This is an attack of the immune system against the organs and tissues of its own body, as a result of which their structural and functional damage occurs.
They can be primary, but more often secondary. More common are secondary autoimmune diseases associated with a partial change in one's own antigens under the influence of toxins, drugs, microorganisms, parasites, with denaturation of proteins in damaged cells, tissues, and other factors, as well as with immunization with antigens of microorganisms that have similar determinants to animal cell antigens.
Etiology. Autoimmune diseases can occur as a result of congenital or acquired disorders in the immune system, accompanied by a loss of tolerance of immunocompetent cells to their own antigens and the appearance of prohibited clones of lymphocytes. The development of autoimmune pathology is possible with 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 a change in their own antigens under the influence of toxins, drugs, viruses, proteolytic processing and denaturation of proteins in damaged cells and tissues. Many autoimmune lesions can occur when immunized with antigens that are common to both bacteria and body tissues. So, in calves and piglets there are similar antigenic determinants of the intestinal mucosa with O-antigens of E. coli, in the epithelium of the intestine and liver - with Salmonella antigens. Various lesions of tissues and organs in animals also develop during the deposition of immune
antigen+antibody complexes.
In newborn young animals, autoimmune diseases occur by the colostral route, when autoantibodies and lymphocytes sensitized against the antigens of certain organs are transmitted to him through the colostrum of sick mothers. In cows and sows, autoimmune lesions of the digestive organs are often recorded, due to 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 impaired immunological homeostasis and the release of autoantigens to which there is no immunological tolerance. Therefore, if the biological barriers of isolation 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 the released intraorganic, intracellular and altered 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 undulating course of the disease. In newborn animals, the disease develops after ingestion of colostrum containing autoantibodies and sensitized lymphocytes. In addition, patients have clinical symptoms characteristic of damage to a particular organ or an entire organ system. Circulating autoantibodies and sensitized lymphocytes are found in the blood. In the period of exacerbation of the disease, autoantigens and immune complexes antigen + antibody can be detected. 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 noted for antigens of the liver, pancreas and much weaker intestines, and in chronic feed intoxications - for the antigen of the mucous membrane of the stomach, 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. Plasma cells containing autoantibodies are often found among the cellular infiltrate. Regional lymph nodes 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, the clinical manifestation of the disease, the results of an 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 lifetime diagnosis of autoimmune diseases. For the detection of antibodies, the reactions of immune diffusion (RID), indirect hemagglutination (RNHA), complement fixation (RSC),
immunofluorescence (RIF), and sensitized lymphocytes of internal
skin allergy test. Filtrates obtained from homogenates of organs of healthy animals are used as antigens. Presence of precipitation bands in RID, agglutination of erythrocytes at a dilution of 1:32 and higher in RNHA, 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 on the injected antigen during intradermal The sample confirms an autoimmune disease.
These reactions can also be used to detect antigens and immune complexes. However, they are more difficult to detect due to their low concentration in biological fluids.
When diagnosing autoimmune pathology, it must be taken into account that organ antigens in the blood, mammary gland secretions and urine are found mainly in the acute course and exacerbation of the chronic process. Their appearance is combined with the development of alternative processes. Following the release of organ antigens, an immune response develops and autoantibodies and sensitized lymphocytes appear. As the processes fade from the blood and other biological fluids, organ antigens first disappear, 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 occurrence of autoimmune diseases of the digestive organs in newborn young animals, due to the transmission of autoimmune factors by the colostral route.
Based on the detection of antigens, autoantibodies and immune complexes, autoimmune diseases of specific organs and systems are differentiated.
The prognosis is cautious.
Treatment. In the complex treatment of sick animals with autoimmune pathology, intramuscular antilymphocytic serum and antilymphocytic globulin are used in a lot of OD-0.2 mg / kg
cortisone, cortisone at 0.5-1.0 Lib/kg and
The necessary treatment is additionally prescribed for the development of the pathology and its complications. .„„--.- th immunopathology reProphylaxis. In i!fouche „„th exchange, voschoot. and nutritional value is underestimated in uterine total intoxications in particular autoimmune dyspepsia. In order to prevent it, a „_pyatyatel and sensitized
origin**?ly of the muscular stomach of birds, lignin, poro.
loziva 2-3 times and adding necessarily
new or whole blood healthy instructions. With a massive non-
prescribe vitamin preparations GT) aza, but after birth they are fed well ^ ^ according to this immunoglobulins, serum
colostrum substitutes, iiikhash, _ yeomah and complexes
“ “-g sravd * e “after
“yalod”;iTz / k.zaVkoy =
in the treatment of autoimmune zaooleVYN™ Scam is not allowed
justified feeding and "P" silted with fungi containing disease-
pouring low-quality cor. , P Gih toxic substances.
unreasonable treatment "she is sick, animals with pronounced alternatives, -
and inflammatory processes of various kinds.