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IMMUNE-MEDIATED DISEASES
The immune system is a complex and intricate collection of cells, tissues and organs that work together with one basic goal in mind: to defend the body from foreign invaders. How this system functions is far beyond the scope of this program and it would be fair to say that despite all we know of the immune system, we still understand very little. As this program is concerned more with abnormal conditions and their treatment, it will be sufficient to say that, at times, this complex system does not perfectly perform its functions and disease results.
For this discussion, there are four basic types of immune-mediated diseases: Hypersensitivity Disorders which include allergic type reactions. Autoimmune Disease wherein the immune system attacks the normal tissues of the individual. Immune Complex Disease which occurs most commonly as antibodies in clumps become deposited in friendly tissues and cause an inflammatory response. Immunodeficiency Disease where the body fails to produce needed levels of protection. Some veterinarians will classify Immune Complex Disease as a Hypersensitivity disorder, but for clarity, we have separated these in this work.
Hypersensitivity disorders can best be thought of as an exaggerated or excessive response by the body to foreign stimuli. In other words, the system is trying to do its job in defending the body, but goes a bit too far. The common hypersensitivity disorders include Angioedema and Urticaria, Atopic Dermatitis, Contact Hypersensitivity, Food Allergy, Flea Allergic Dermatitis and Miscellaneous Allergic Reactions.
Angioedema is most often characterized by signs of sudden swelling of an area, often the face, where fluid leaks out of the blood vessels into the surrounding tissues. (edema) The dog may or may not seem itchy, but many times will scratch at the area or rub the face on the floor. The swelling may come on quickly and progress rather rapidly. ((Facial Swelling))
Urticaria can best be thought of as "hives", more properly called wheals or little bumps and swellings that occur in various locations on the skin. These too will appear suddenly and may persist for some time, or seem to disappear and reappear again. These hives may or may not be itchy for the dog. ((Hives))
Sudden reactions to insect bites and inhaled pollens are considered the usual initiating factors, but reactions to foods, bacteria, chemicals, drugs, vaccinations and parasites among others can set these reactions into full swing. Both conditions may be very irritating to your pet and angioedema can be life threatening if swelling of the throat or fluid leakage into the lungs occurs. Diagnosis is based on history and obvious clinical signs.
TREATMENT OF ANGIOEDEMA AND URTICARIA
Rapid attention in all cases of angioedema is advised, as it is difficult to determine which reactions will become life threatening and which will not. All cases should be treated to comfort the dog. The use of injectable cortisone, epinephrine and antihistamines will quickly reverse the reaction, with a few days of cortisone and/or an antihistamine often used to prevent immediate recurrence. If a dog has had a reaction to a bite or vaccination this does not mean that this reaction will occur again, as these tend to be sporadic and unpredictable reactions.
ATOPIC DERMATITIS (CANINE ATOPY, ALLERGIC DERMATITIS)
Atopy is the most common form of allergic reaction, producing the usual symptoms of "allergies" in the dog. Certain breeds seem to be more prone to Atopy, including the West Highland White Terrier, Scotties, Boston Terriers, Miniature Schnauzers, Pugs and Dalmatians, but many and all breeds can be affected. Dogs with allergies will usually start showing symptoms between 1-3 years of age but symptoms can begin any time, at any age, without prior history of such.
Allergic Dermatitis is caused when an allergen is inhaled or otherwise absorbed into the body and an allergic reaction begins. The most outstanding clinical sign will be that of pruritus, which is the medical term for itching! Itching of the back, flanks and face is common, as is licking of the feet or groin areas. The itching may progress and include other skin areas such as the eyes and ears. While this pruritus is the main clinical sign, as the dog scratches, rubs or licks the areas involved, hair loss, skin infections, redness or seborrhea may occur as secondary problems. This type of allergy may also be seasonal.
Some dogs will exhibit non-dermatologic symptoms including sneezing, troubled breathing, coughing and bowel and bladder trouble but these symptoms are less common and will usually be in conjunction with obvious skin disease. It is important to note that not all dogs will have all the symptoms or areas affected and often the itching is passed off by the owner until secondary problems due to self trauma, such as a skin infection, become apparent. Diagnosis is based on the clinical signs, history, the use of intradermal skin testing, RAST testing and skin biopsy. Other conditions causing itching should be carefully ruled out. ((Allergic Dermatitis))
TREATMENT OF ALLERGIC DERMATITIS
Ideally, avoiding whatever the dog is allergic to would solve the problem. Practically, unless your veterinarian does the more extensive testing, you will only be able to guess at the cause making avoidance very difficult. Also, with the allergens most often being airborne and inhaled, the practicality of such a plan is poor.
The use of prednisolone or triamcinolone, steroidal drugs, is most often employed. The doctor will often give an injection first, then follow up with oral medication. These drugs work best because they not only stop the allergic reaction, but they relieve the skin inflammation and thusly, the itching. For long term use, however, these drugs should be avoided or restricted to avoid side effects.
Antihistamines can be used, but their effect is minimal in most cases of canine allergies and these should be considered helper drugs. Fatty acid supplements such as Derm Caps and EFA Caps and special non-allergenic diets are also useful. These can sometimes provide moderate relief without all the effects of cortisone. Your veterinarian will provide several suggestions for these and you should expect to have a trial period of 60-120 days to be able to determine how useful this type of therapy can be.
Medicated shampoos, antibiotics and other treatments may be needed if secondary skin disease and self-trauma have occurred. If your dog has been allergy tested and the offending substances identified, hyposensitization therapy can be undertaken. This involves giving injections from a series of treatment solutions designed to meet your dog's allergy profile for a period of several months, then on a regular basis to maintain the effect. This treatment often works well, but is not without possible complications including total failure or an exacerbation of the allergic symptoms.
A newer form of therapy involves using a drug called Atopica, an immune modulator that helps your pet’s body not over-react when it encounters an offending allergen. Success and safety of this drug is proving to be very good.
Contact allergy is relatively rare. People often think their dog became itchy from touching the grass or from shampoo at the grooming shop when in reality, if an allergic reaction is occurring, it is most probably atopic. Contact allergy has been reported after contact with certain plants, topical medications, chemicals, chlorine and materials found in the home such as food bowls and fabrics.
Clinical signs include skin irritation between the toes, on the chest and abdomen, chin, groin and genital areas. The amount of itching will vary greatly, and secondary redness, small bumps forming in the area, changes in pigmentation and crusting of the skin may also all be present. Careful history, physical exam and testing to rule out other skin diseases is essential for diagnosis. A "patch" test is the only reliable and definitive test, but is rarely undertaken due to difficulty with the actual procedure.
TREATMENT OF CONTACT HYPERSENSITIVITY
Injectable and oral prednisolone or triamcinolone is often very effective. Most dogs will respond well and quickly return to normal. Antibiotics and shampoos may be needed if secondary problems are present. Avoidance of the allergen(s) in question, if identified, is the best form of therapy.
Food allergy is relatively uncommon, but it can cause significant pruritic dermatitis in the dog. Allergens in food also seem to contribute in cases of atopic dermatitis. Any dog can be affected, even from food they have eaten for long periods of time and the problem will not be seasonal. Food allergy may also be confused with other skin problems and some veterinarians may be slow to consider it in making a diagnosis. ((Food Allergy))
Clinical signs will include itching, licking the feet, hives, redness, crusting and scaling of the skin. There is, however, no classical case of food allergic dermatitis. If the itching is treated with cortisone, though, most dogs will not respond as well as if they had simple atopic dermatitis and this may be a clue in diagnosis. Often pruritus of the ears, seborrhea and vomiting and/or diarrhea will concurrently be present. Diagnosis is based on history, clinical signs, ruling out other diseases, evaluation of the response to prednisolone therapy and allergy testing. Most often, diagnosis will be based on a therapeutic trial with a special diet over a period of time. Several special diets are now available through your veterinarian, but the process may indeed be one of trial and error. A dog needs to be on the special food for several weeks to determine if the desired response will be had.
TREATMENT OF FOOD ALLERGY
After a determination has been made that your dog has food allergy and by trial and error, a diet has been selected, long-term use of the special food and avoidance of other treats and table foods can be very effective. The use of prednisolone or antihistamines may help in more difficult cases. Some owners and veterinarians prefer to improvise homemade diets and if so, special care needs to be given to formulation to insure essential nutrients are not omitted.
Fleas in and of themselves cause a very itchy bite. When they bite, a small amount of flea saliva is secreted under the skin and in some dogs, will cause a very intense allergic reaction. Any dog can be affected and in some cases where multiple dogs are in an area and have fleas, only one will develop an allergic reaction to the flea saliva.
Clinical signs include the presence of fleas, extreme and intense itching, redness of the skin, loss of hair often on the back, rump and flank areas and secondary infections of the skin. A crusty, scaly dermatitis with a fetid odor can occur later in the course of the disease. Diagnosis is based on these clinical signs and finding the fleas or evidence of their presence (flea dirt etc.). A specific flea allergen test is available and may be advised in some circumstances. Most of the time, with these signs and finding the flea, the diagnosis will be flea allergic dermatitis until proven otherwise. ((Flea Allergic Dermatitis))
TREATMENT OF FLEA ALLERGIC DERMATITIS
Control of the Flea, like any other form of avoidance therapy, is paramount to solving this condition. As only one fleabite can trigger major clinical signs in the allergic dog, even the smallest infestation can cause the biggest of problems for the dog. This means that environmental extermination should take top priority in the treatment program.
The use of prednisolone or triamcinolone, first as an injection and then orally, is very effective in curbing the allergic reaction, but oral medication must be used until all fleabites have stopped. Antihistamines, medicated shampoos and fatty acid supplements can all be used to speed healing and antibiotics may be needed of secondary infections have occurred.
MISCELLANEOUS ALLERGIC REACTIONS
Hypersensitivities to drugs, a dog's own hormones, sarcoptic mange, ticks, internal parasites, ear mites, heartworms, bacteria and fungi have all been reported. While most of these conditions are rare, it is important to note that allergic reactions can happen against a many various causes. Although these are rare conditions and not a typical diagnosis, they may be suspect in cases where drug administration is present or parasitic disease has been diagnosed. Clinical signs will always include some degree of itching, with secondary areas of infection, crusting and hair loss. Diagnosis depends highly on historical information and related diagnosis.
TREATMENT OF MISCELLANEOUS ALLERGIC REACTIONS
Diagnosis of the primary problem and treatment of that will do the most to relieve the clinical signs. Antibiotics, removal of drug therapy and parasitic dips are appropriate for their specific conditions. Prednisolone or triamcinolone, antihistamines and medicated shampoos are commonly employed to soothe and heal the skin.
Autoimmune disease can literally be thought of as the body attacking itself. This is a rare occurrence which may be due to a loss of "self-tolerance", for reasons poorly understood, or it may occur secondarily as the body is trying to attack a foreign invader but mistakenly starts producing immunity to normal body cells. This type of reaction is seem commonly in dogs with ehrlichiosis, a blood parasite; many will develop autoimmune hemolytic anemia, a destruction of blood cells by antibodies in the system. These processes are still poorly understood as science is just now beginning to explore the immune system.
Pemphigus involves a set of diseases whereby antibodies have been formed against skin cells. These conditions are rare and are characterized by cracks, blisters and ulcers of the skin.
PEMPHIGUS FOLIACEUS is the most common form of the disease seen in dogs. It is highly variable on how it will appear, how severe it will become and how uncomfortable the patient will be. Most dogs will develop the disease before the age of 5, having had several years history of pruritic skin disease. The skin on the nose, face, ears, feet and groin is most commonly involved, but may progress to cover larger areas of the body. The disease begins as small red spots that turn into pustules, swellings that contain pus and then rupture and turn crusty.
Four common clinical syndromes/variations are noted to occur:
Pemphigus Erythematosus, Pemphigus Vulgaris, Pemphigus Vegetans and Bullous Pemphigoid.
PEMPHIGUS ERYTHEMATOSUS is considered a mild or more benign form of pemphigus foliaceus seen as red, raw pustules on the face and ears. It is quite rare.
PEMPHIGUS VULGARIS is very rare. Clinical signs include blisters and ulcers of the lips, eyelids, ears, nose, genital areas and anus. Most dogs will have lesions on the mouth and lips and may have a foul oral odor and salivation.
PEMPHIGUS VEGETANS is also a very rare variation; blisters and pustules which appear on the body later turn into small wart-like growths.
BULLOUS PEMPHIGOID which is very rare causes blisters and ulcers of the mouth, body and genital areas in various degrees and combinations.
Diagnosis of this complex of diseases is based on history, clinical signs, cytology of exudates, cultures and blood testing. The most important diagnostic test is performing a skin biopsy followed by special pathologic testing. ((Lip Ulcers))
TREATMENT OF PEMPHIGUS
Early and aggressive treatment with prednisolone is considered the mainstay of therapy, but therapy should be based and extended in correlation with the severity of the lesions and the discomfort of the canine. Other treatments include the use of aurothioglucose, a gold salt, azathioprine and cytoxan. All these medications including prednisolone can have side effects so careful patient monitoring by your veterinarian is very important. Antibiotics and medicated shampoos are also used to treat secondary infections and soothe and cleanse the skin.
AUTOIMMUNE HEMOLYTIC ANEMIA (IMMUNE-MEDIATED HEMOLYTIC ANEMIA)
This disease is characterized by a sudden and often devastating destruction of red blood cells within the circulatory system. It is caused when antibodies attach to the surface of red blood cells and trigger their destruction. Poodles and Old English Sheepdogs seem to have a higher incidence of the disease but AIHA can occur in any dog. Rarely will dog owners recognize this as having occurred as usually only more general symptoms are present including fever, weakness, lethargy and poor appetite. Some dogs will vomit and/or have diarrhea; icterus (yellow gums/sclera) may be noted and/or the gums may seem quite pale. ((Pale Gums))
It is possible to have a hemolytic anemia that is not immune-mediated. Drugs, chemicals, plant poisons, cancers and metabolic disease can all lead to blood destruction and the symptoms previously described. Other than the initiating cause being different, the clinical signs, diagnosis and treatment will all be the same as for dogs with AIHA.
Diagnosis will be based on history, physical exam where the doctor may also detect an enlarged spleen or liver, rapid heart and respiration rates, as well as blood tests including blood counts, serum chemistry, urinalysis and special testing to detect the enemy antibodies, known as a Coombs test. The disease may be seen concurrently with immune-mediated thrombocytopenia and SLE or secondary to parasitic blood disorders such as ehrlichiosis and hemobartonellosis, so diagnosis should be thorough as to not miss these other problems.
TREATMENT OF AUTOIMMUNE HEMOLYTIC ANEMIA
The first goal of treatment is to stop further red cell destruction and stabilize the patient. Most dogs will need hospitalization with intravenous fluid administration. Intravenous steroids will be injected, then oral steroids thereafter. Cimetidine is also given to help prevent gastric ulceration due to the steroids. Danazol can also be used but the cost is somewhat high. Cyclophosphamide, an immunosuppressive drug, is employed in some cases. Blood transfusions are given to some dogs, but these should be reserved for cases where blood counts have dropped to dangerous levels. Removal of the spleen is also performed on occasion, but this too should be approached with caution.
If treatment is started early and there are few systemic side effects, the prognosis can be quite good, even in the long term. If organ damage or other immune mediated disease is present, the prognosis is then somewhat poor. Some dogs can be put into complete remission and live a very normal life.
IMMUNE-MEDIATED THROMBOCYTOPENIA
This disease is very similar to autoimmune hemolytic anemia, except those antibodies attack the platelets, the blood clotting cells in the circulation. Poodles and Old English Sheepdogs seem to have a higher incidence of the disease. Clinical signs of this disease present by itself include nose bleeds, black, tarry stools, small hemorrhagic spots on the gums or on the skin and possibly spitting up blood or passing blood in the urine. Diagnosis is made from physical findings, blood counts, serum chemistries, urinalysis, special tests to measure how the blood clots and taking a biopsy of the bone marrow.
TREATMENT OF IMMUNE MEDIATED THROMBOCYTOPENIA
Treatment initially is similar to that of autoimmune hemolytic anemia: hospitalization with intravenous fluid administration, intravenous steroids, then oral steroids thereafter and administration of cimetidine and danazol. The use of a drug called vincristine with or without a platelet transfusion may also be helpful. Splenectomy may be performed but should be reserved for refractory cases.
MISCELLANEOUS IMMUNE-MEDIATED DISEASE
Several other diseases have been described where the immune system attacks specific organs and often produces disorders specific to malfunction of that organ and not specific for immune disease. These include immune-mediated hypothyroidism, diabetes mellitus, polymyositis and eosinophilic myositis both muscle diseases, myasthenia gravis and polyradiculoneuritis diseases causing weakness as the immune system attacks the nervous system and conjunctivitis, meningitis and orchitis among others.
IMMUNE COMPLEX DISEASE
Immune complex diseases are caused as groups or clumps of antibodies are deposited in certain tissues and inflammation occurs in those tissues or organs.
SLE is an uncommon and difficult disease to diagnose because so many differing and variable clinical symptoms may occur, with SLE often resembling some other specific problem. Antibodies against specific tissues are formed and attack those organs. Clinical signs include arthritis in multiple joints, fever, decreased red blood cell counts (anemia), skin disease and ulcers of the mouth and lips. Disease of the spleen, heart, lungs, nervous system and other organs can also occur. To reiterate, there is no specific or single group of symptoms that characterize this disease. ((Lip Ulcers))
Diagnosis is challenging to say the least. Besides history and clinical signs, blood counts, serum chemistries and special tests for immune mediated disease, including SLE should be performed. Skin biopsy may be useful if lesions of the skin are present. Hopefully the veterinarian will have an instinctive feel that SLE may be the primary condition and search accordingly.
TREATMENT OF SYSTMIC LUPUS ERYTHEMATOSUS
Treatment success for SLE is also variable and unpredictable and will most often depend on the severity of the disease at the time of diagnosis. Otherwise, treatment is similar to that of other immune mediated diseases: oral prednisolone in high doses to start and the use of azathioprine or chlorambucil if that proves unsatisfactory. Management of secondary infections or hemolytic anemia will also be needed if these are present concurrently. The response to therapy will vary, some dogs living long term in remission, others dead or euthanised due to complications and relapses in less than a year.
DISCOID LUPUS
Discoid lupus seems to be a benign, localized form of SLE. Most dogs exhibit loss of pigment from the nose, followed by crusting and scaling. The area may appear quite red and raw. Later, erosions and ulceration of the nose and nearby skin will be noted. Involvement of other body systems does not occur. The condition will occur more often in outdoor dogs secondary to exposure to UV light.
TREATMENT OF DISCOID LUPUS
All cases will benefit by keeping the dog out of the sun. Sunscreens applied to the nose and/or cortisone creams also seem to be of benefit. Oral vitamin E (only as directed by a veterinarian) and prednisolone will in most cases be effective in the long term.
Glomerulonephritis (immune-mediated inflammation of part of the kidney) occurs when the body produces antibodies against the glomerulus or when complexes (clumps) of antibodies get deposited in the glomerulus. This alters the functional ability of the filtering section in the kidney leading to loss of protein in the urine, a decrease of protein in the blood, an increase in blood cholesterol and fluid collecting in areas of the body (edema). Progressive kidney damage usually occurs leading to renal failure. Clinical signs include loss of weight, swelling of the limbs, fluid collection in the abdomen, legs and possibly the lungs. If renal failure occurs, those clinical signs also occur and most dogs will die. Diagnosis is based on these signs, blood and urine tests and a biopsy of the kidney.
RHEUMATIOD ARTHRITIS
Immune complexes attacking the joints and surrounding tissues cause what is known as rheumatoid arthritis, uncommon in the dog. Gross erosion of the joint cartilage and bone tissue can occur and the normal space within the joint will narrow greatly. Onset of the disease if often sudden, starting when the dog is 4-6 years old on average. Symptoms include lameness that seems to change legs and cause a shortened stride, swollen joints, lethargy and fever.
Diagnosis is based on history, physical signs, X-rays, biopsy of the joints and analysis of the fluid within the joints, called synovial fluid, which is obtained by suctioning fluid from a joint through a needle. Blood counts, serum chemistries and special serological tests are also often used to make the final diagnosis and rule out other immune mediated diseases.
TREATMENT OF RHEUMATIOD ARTHRITIS
This disease is difficult to cure, but most dogs will improve and stay relatively comfortable with therapy. The use of aspirin, Arquel or Rimadyl for pain and prednisolone to suppress the immune reaction will be the first approach your veterinarian will use. Stronger immunosuppressive drugs like cyclophosphamide, azathioprine and gold salts are employed in more difficult cases. Weight loss and proper exercise is advised for all patients and Adequan, Cosequin or similar products may help heal the joints if erosion has occurred. While considered safe, these are unproven treatments.
VASCULITIS, inflammation of the blood vessels, can occur when immune complexes are deposited on the walls of veins and arteries. Clinical signs can be similar to SLE, or can also include small hemorrhagic spots on the skin, ulcers and symptoms similar to urticaria. The condition is rare and diagnosis is based on physical examination, blood and urine tests, biopsy of affected areas and special serological tests. Treatment is similar to that for pemphigus. ((Petichia))
IMMUNODEFICIENCY DISEASE
There are two basic classifications of immunodeficiency disease: primary, meaning belonging to the dog and secondary, meaning caused by something else. These are uncommon problems so the discussion herein will be for informative purposes only.
The most common primary immunodeficiency is called transient hypogamma-globulinemia of puppies; a delay in the normal beginning of antibody production in young dogs which leaves them more susceptible to illness. Often seen between 2-5 months of age, dogs that do not contact severe illness will naturally be cured as their immune system fully develops. Respiratory disease, which is not infrequent in these dogs, should be treated accordingly.
Secondary immunodeficiency or immunosuppression has been well documented in cases of canine distemper, canine parvovirus, demodicosis and some recurrent cases of pyoderma. Puppies that fail to receive adequate colostrum, antibodies transferred from mother to pups in the milk will be more susceptible to disease for their first 2-3 months of life until their own immune system begins working.
