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Disorders Involving Cytotoxic Antibodies (Type II Reactions) in Dogs

By Christine Andreoni, , Senior Manager, Department of Immunology, Discovery Merial Limited ; Kevin T. Schultz, DVM, PhD, Chief Scientific Officer, Head of Global Research and Development, Merial Limited

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Type II reactions can lead to several types of diseases in dogs, including anemia, blood clotting problems, and skin and muscle disorders. They may be associated with other immune system disturbances, such as systemic lupus erythematosus, or triggered by a drug, vaccine, or infection. Most often, the triggering cause cannot be pinpointed. Immune-mediated hemolytic anemia and thrombocytopenia are the most common Type II reactions.

Immune-mediated Hemolytic Anemia

This type of anemia is a severe and life-threatening disease in which the dog’s immune system sees its own red blood cells as foreign invaders, and therefore produces antibodies to destroy them. Red blood cells are manufactured as usual in the bone marrow, but once released into the bloodstream, they are attacked and destroyed by antibodies. Signs of anemia may include fatigue, paleness of the lips and gums, and depression, along with jaundice in some cases. Other signs your veterinarian may find include an enlarged liver or spleen.

Immune-mediated hemolytic anemia has 4 basic forms, peracute, acute or subacute, chronic, and pure red cell aplasia. Most forms are treatable with medications, including corticosteroids and cytotoxic drugs (such as those often used in chemotherapy). Relapses are uncommon.

Immune-mediated Thrombocytopenia

Immune-mediated thrombocytopenia is common in dogs and occurs more often in females than males. This condition is caused by the destruction of platelets (thrombocytes) by the immune system in much the same manner as red blood cells are destroyed in immune-mediated hemolytic anemia (see Disorders Involving Cytotoxic Antibodies (Type II Reactions) in Dogs : Immune-mediated Hemolytic Anemia). When an animal has thrombocytopenia, clotting does not occur correctly. Even minor injuries can cause uncontrollable bleeding, further decreasing the number of red blood cells. The most frequent signs are bleeding of the skin and mucous membranes.

Before immune-mediated thrombocytopenia can be diagnosed, many more common diseases must be excluded, including various clotting disorders, bladder or prostate infections or cancer, and intestinal parasites. The diagnosis is usually made based on signs and response to treatment, rather than on blood tests. However, certain blood tests such as platelet counts and clotting profiles are helpful. Medication will likely be prescribed to treat this disease. Signs usually disappear after 5 to 7 days of treatment when platelet counts begin to rise. If the platelet count has not increased significantly after 7 to 10 days, additional or different medications may be prescribed. If the blood loss is life threatening, transfusions of whole blood or plasma may be necessary.

Treatment is often continued for 1 to 3 months after the platelet counts return to normal. Some dogs have persistent decreases in platelets even with drug treatment. If this is the case with your pet, you and your veterinarian will want to discuss longterm treatment and maintenance options.

Autoimmune Skin Disorders

Pemphigus foliaceus is an uncommon autoimmune disease that affects the skin. The cause of this malfunction of the immune system is usually not known. One theory is that the skin is somehow altered, making it appear “foreign” to the immune system. In the case of pemphigus foliaceus, the immune system produces antibodies against the “glue” that normally keeps skin cells (keratinocytes) attached to one another. White blood cells move in causing further damage, and the keratinocytes break apart from each other, forming pimples or crusted areas. Veterinarians frequently prescribe corticosteroids for initial treatment of pemphigus foliaceus, but other immunosuppressive drugs may be added if there is no response.

Pemphigus vulgaris is a very rare disease in dogs. It produces mouth abnormalities, but other areas of the skin are only mildly affected. The disease is often controlled with high doses of corticosteroids in combination with other drugs that suppress the immune system.

Bullous pemphigoid has been seen in Collies and Doberman Pinschers. Abnormalities are often widespread but tend to be concentrated in the groin. The involved skin resembles a severe scald and may include blisters. The disease is usually treated with corticosteroids, but continuous treatment is often needed and the longterm outlook is poor.

Myasthenia Gravis

Myasthenia gravis is an autoimmune neuromuscular disease seen in both people and animals, including dogs. It can be congenital (present at birth) or immune-mediated, developing later in life. Weakness is the primary sign. Affected animals produce antibodies to certain nerve receptors and destroy them. This leads to the inability to contract muscles and extreme muscle weakness. In older dogs, the first sign of problems may be an enlargement of the esophagus (megaesophagus) due to the muscular weakness. The enlargement of the esophagus leads to problems with swallow-ing. This can cause regurgitation which may, in turn, cause inhalation pneumonia. Myasthenia gravis is diagnosed using blood tests to search for the antibody to the nerve receptor and other tests for nerve activity. Your veterinarian will prescribe drugs to control this disease. Remissions can occur, and many dogs that develop this condition do well with continued treatment.

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