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Old 07-21-2009, 05:06 PM
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Default Re: Autoimmune disorder in cats - advice needed!

taken from http://www.provet.co.uk/petfacts/hea...unedisease.htm

AUTOIMMUNE DISEASES

Note for Pet Owners:

This information is provided by Provet for educational purposes only.

You should seek the advice of your veterinarian if your pet is ill as only he or she can correctly advise on the diagnosis and recommend the treatment that is most appropriate for your pet.

Topics on this Page: Description
Cause
Breed Occurrence
Signs
Complications
Diagnosis
Treatment
Prognosis




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Description
In nature animals have evolved a sophisticated defence system that produces glycoproteins called immunoglobulins or antibodies in response to chemicals (antigens) on the surface of organisms (eg bacteria, viruses) or other substances (eg toxins) that gain access to the body. The antibodies chemically bind with the antigens - an initial step in the process to remove them from the body.

Under normal circumstances the body's immune system recognises tissues and cells that are part of itself, and the immune system will only produce antibodies against foreign cells. However, sometimes the controlling mechanisms fail and the immune system does produce antibodies which attack the animals own body tissues. These are called autoantibodies and the disease that results is called an autoimmune disease.

Autoantibodies may be formed against specific organs or specific types of cell (eg blood cells), or they may be non-organ specific. In the last category antibodies are often produced which act against nuclear material within the nucleus of cells and these are called antinuclear antibodies (ANAs). ANAs are commonly found in some forms of autoimmune disease eg systemic lupus erythematosus (SLE)


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Cause
The cause of autoimmune diseases is the production of autoantibodies against the animals own tissues. The underlying reasons for these disorders occurring are complex and not fully understood.

Infectious agents are thought to be the initiating factor in some of these disorders eg Systemic Lupus Erythematosus (SLE)


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Breed Occurrence
There are several reports of possible increased incidence of autoimmune diseases in some breeds and sexes :

Cocker Spaniels,Old English Sheepdogs and Poodles may be predisposed to develop autoimmune haemolytic anaemia
Poodles are over-represented in reports of autoimmune thrombocytopenia
Female dogs more often develop autoimmune haemolytic anaemia, and autoimmune thrombocytopenia than males
Poodles and German Shepherds may be predisposed to develop Systemic Lupus Erythematosus
Toy breeds of dog may be predisposed to develop rheumatoid arthritis

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Signs

The common signs of autoimmune disease in animals depend upon the target organ(s) for the autoantibodies :

Adrenal gland

Some cases of canine hypoadrenocorticism (Addisons disease) are due to autoantibody production against the adrenal glands.
Signs include :
Muscle weakness - the dog collapses during exercise
Depression
Sudden collapse and shock
Kidney failure
Inappetance
Diarrhoea - sometimes contains blood
Abdominal pain
Increased thirst (polydipsia)
Increased urine production (polyuria)
Weight loss
Blood

Autoimmune haemolytic anaemia (dogs, cats (rare - often secondary to leukaemia), cattle (very rare), horses (rare - usually secondary eg abscesses). It can occur with autoimmune thrombocytopenia.
Due to autoantibodies against the animals own red blood cells causing them to disrupt (called haemolysis)
Coombs test is positive in these patients
Anaemia may be present on routine haematological examination
Free haemoglobin is present in blood and urine
The animal may develop jaundice (accumulation of yellow pigment in tissues)
Affected animals are lethargic
Extremities (ears, feet, nose and tail) may become blue (cyanosed) or reddened, swollen, ulcerated and crusts may form.
Enlargement of the spleen may occur
Enlargement of lymph nodes may occur
Sometimes autoimmune haemolytic anaemia has a primary cause eg it can be induced by drugs
Autoimmune thrombocytopenia (dogs, cats (rare), horses. It can be secondary to systemic lupus erythematosus - see below). It can occur with autoimmune haemolytic anaemia
Due to autoantibodies against platelets which are important in blood clotting.
Haemorrhages into the skin (small petechial haemorrhages, larger ecchymotic haemorrhages (patches) or sometimes massive haemorrhages - nose bleeds or internal bleeding into the abdomen or chest )
Systemic lupus erythematosus (SLE) - see below
Musculoskeletal System

Myasthenia gravis (dogs and cats)
The acquired form of this disease is associated with the production of autoantibodies against acetylcholine receptors on muscle. Signs include :
Poor exercise tolerance
Muscle weakness
Difficulty eating and swallowing
Regurgitation of food
Dilation of the oesophagus (megaoesophagus)
Rheumatoid arthritis - Autoantibodies against IgG are associated with rheumatoid arthritis the signs of which are :
Lameness
Swollen joints - often affects the same joints in the left and right limbs.
Restricted range of movement in joints, and in advanced cases there may be no movement in the joint
In some cases the joint dislocates because local ligaments rupture, and so there is an excessive range of movement
Crepitus (a grating sensation and clicking or cracking sound) is present when the joints are manipulated
High body temperature
Inappetance
Systemic lupus erythematosus (SLE) - see Multiple organ autoimmune diseases below.
Skin

Bullous Autoimmune Skin Disease
Pemphigus vulgaris (dogs and cats)
Erosions or ulcers around the mucocutaneous junctions (mouth, nails)
The lesions discharge serum and crusts form over the ulcers
Depression
Inappetance
Death
Pemphigus foliaceus (most common canine and equine autoimmune skin disease, also reported in cats and goats)
Small swellings under the surface of the skin (bullae or pustules)
Crusting
Scale (scurf or dandruff) formation
Loss of hair (alopecia)
Black pigmentation of the skin (hyperpigmentation)
Sloughing of the foot pads
Itchiness (pruritus)
Usually affects the head and nose, but can be generalised
Pemphigus vegetans (rare- dog))
Pustules
Crusting
Papilloma formation
Can be generalised or in the groin area
Pemphigus erythematosus (dog and cat)
Discharging sores
Crusting
Itchiness (pruritus)
Affects mainly the skin around the eyes, the ears and on the bridge of the nose.
The disease gets worse if the skin is exposed to sunlight
Bullous pemphigoid (dog and horse)
Erosions or ulcers around the mucocutaneous junctions (eg lips and mouth), the ears or the groin
The lesions discharge serum and crusts form over the ulcers
Depression
Inappetance
High body temperature - due to secondary infection
Thyroid

Autoantibodies against thyroglobulin (and occasionally against thyroid hormone T3) are associated with lymphocytic thyroiditis - the main cause of hypothyroidism in dogs. Signs of hypothyroidism include :
Bilateral hair loss (alopecia)
Thinning of the skin
Lethargy
Black pigmentation of the skin
Scurf (dandruff)
Lethargy
Obesity
Cold intolerance - seeks warm places to lie down
Reproductive problems.
Fat deposits in the cornea of the eye (lipidosis)
Dry eye (keratitis sicca)
Diarrheoa
Vomiting
Constipation
Slow heart rate (bradycardia)
Muscle weakness
Multiple Organ Autoimmune Diseases

Systemic lupus erythematosus (SLE) - (dogs and cats)
Arthritis (rheumatoid) in several joints - see above - most common presenting sign
Skin disease - second most common presenting sign
Bilaterally symmetrical loss of hair and production of scurf (scale or dandruff)
Ulcerations and crusting form in severe cases - often affecting the ears, feet and head
High body temperature - does not respond to antibiotics, does respond to corticosteroids (present in over 50% of cases)
Inappetance
Anaemia - causes lethargy. Positive Coombs test.
Thrombocytopenia (low platelet count - less than 50,000 per cubic mm - present in about 30% of cases) - may lead to haemorrhages
Neutropenia - low white cell count (neutrophils) (present in up to 50% of cases)
Kidney disease - glomerulonephritis (in about 25% of cases) - protein leaks into urine.
Weight loss
High total serum protein

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Complications
Multiple organ system involvement is common and this can make diagnosis difficult.


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Diagnosis
Diagnosis depends upon tests to identify the circulating antibodies, or antibody-antigen complexes that form and other tests specific to the organ involved ;


Adrenal gland

Adrenal insufficiency (Addisons disease)
Indirect immunofluorescence tests
Low blood cortisol concentrations (below 35 nmol/l)
Low plasma sodium concentration (less than 135 mmol/l)
High plasma potassium concentration (over 5.5 mmol/l)
High blood calcium concentrations (in about 50% of cases)
High blood urea and creatinine (about 75% of cases)
Poor ACTH stimulation test
Histopathological examination of adrenal biopsy
Blood

Autoimmune haemolytic anaemia
Coombes test positive
Autoimmune thrombocytopenia
low platelet count (less than 40,000/cubic mm)
Sometimes prolonged ACT (activated coagulation time)
Immunofluorescence tests
ELISA test
Musculoskeletal system
Myasthenia gravis
Immediate response to therapy with 0.1-1.0 mg edrophonium chloride (an anti-cholinesterase drug)
Rheumatoid arthritis - diagnosis is difficult
Rheumatoid Arthirtis (RA) factors may be present on serology - titre needs to be 1:16 or higher
Synovial fluid examination - white blood cell counts exceed 3,000/ cubic mm and can be very high.
Histopathological examination of synovial membrane biopsies.
Radiological findings :
Loss of joint space (due to loss of articular cartilage)
Soft tissue swelling
Radiolucent areas in subchondral bone - typical findings
Other secondary changes eg DJD, ankylosis, luxation
Multiple organ systems
Systemic lupus erythematosus (SLE)
Positive ANA assay test - low titres may be present in NORMAL dog serum - so care is needed in interpretation.The titre should be higher than 1:100.
Positive LE cell preparation
Thyroid

Lymphocytic thyroiditis
Clinical signs
Low thyroid hormone (thyroxine - T4) concentrations in the blood
Histopathological examination of thyroid biopsy
Detection of antithyroglobulin antibodies in plasma

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Treatment
Treatment depends upon the organs involved . The aim is usually to reduce the immune response, however it should be remembered that this will also reduce the animals resistance to infection, so secondary complications may occur.

Adrenal gland

Addisons disease
Emergency treatment to replace fluids and electrolytes
Long term treat with mineralocorticoids eg fludrocortisone acetate at 0.1mg/kg body weight per day AND glucocorticoids eg prednisolone at 0.1-0.3mg/kg body weight per day
Blood

Autoimmune haemolytic anaemia
Immunosuppressive drugs eg
High dose corticosteroids - prednisone or prednisolone at 2mg/kg body weight twice daily by mouth
Cyclophosphamide - in acute, severe cases - 1.5-2.5mg/kg body weight daily by mouth
Blood transfusion - may be beneficial but controversial as haemolysis (disruption of the red cells) may occur
Removal of the spleen (splenectomy)
Treat any primary cause eg remove drug therapy if it is a drug-induced problem
Autoimmune thrombocytopenia
Immunosuppressive drugs :
High dose corticosteroids (see above)
Vincristine - 0.01-0.025mg/kg body weight intravenously every 7 days until platelet counts are normal
Cyclophosphamide - in severe cases - see above
Blood transfusion - severe cases
Splenectomy - if recurrent or non-responsive
Treat any primary cause eg drug-induced problem
Musculoskeletal system

Myasthenia gravis
Cholinesterase inhibitors eg pyridostigmine bromide at 10-60mg three times daily
Corticosteroids eg prednisone at 2-3mg/kg body weight per day
Rheumatoid arthritis
Aspirin - for its anti-inflammatory/analgesic effects - but not if SLE or thrombocytopenia are present
High dose corticosteroids (with/without aspirin) - see above
Cytotoxic drugs :
Azathioprine - 2mg/kg body weight daily or on alternate days or in combination with cyclophosphamide
Cyclophosphamide - 2 mg/kg body weight daily for 4 days per week
Gold salt therapy - 1mg.kg body weight of sodium aurothiomalate every week
Systemic lupus erythematosus - see below
Enteropathic arthritis
Polyarthritis associated with inflammatory bowel disease has been reported to occur in dogs
Multiple organ autoimmune disease

Systemic lupus erythematosus (SLE)
High dose corticosteroids - see above
Azathioprine - for long term treatment
Cyclophosphamide - see above
Vincristine - if thrombocytopenia is present - see above
Skin

Bullous autoimmune skin diseases
Drugs to suppress the immune response. Combinations of these are often given together :
Corticosteroids - eg prednisone or prednisolone 1-2mg/kg body weight by mouth twice daily
Cytotoxic drugs
azathioprine 2mg/kg body weight daily or on alternate days OR
cyclophosphamide 2 mg/kg body weight daily for 4 days per week
Gold salt therapy - 1mg.kg body weight of sodium aurothiomalate every week
Megestrol acetate (cats only)
Avoid exposure to sunlight (cases of pemphigus erythematosus)
Thyroid

Lymphocytic thyroiditis
Synthetic thyroid hormone (T4) replacement therapy

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Prognosis
In autoimmune diseases the prognosis is always guarded with only fair to poor chances of long term survival without treatment. However some respond well to therapy. Some examples are:

Autoimmune thrombocytopenia - prognosis is good if treated aggressively
Bullous autoimmune skin diseases - can often go into remission and be controlled with drugs.
Canine hypothyroidism due to lymphocytic thyroiditis can often be controlled well with thyroid hormone replacement therapy
Myasthenia gravis - prognosis is guarded. Some can undergo remission and be controlled, others progress and die
Systemic lupus erythematosis - prognosis is fair
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The greatness of a nation and its moral progress can be judged by the way in which its animals are treated ~ Mahatma Gandhi
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