Polish Lowland Sheepdog - Pons - Pon the dog
Bliksemdewarrigewite, Netherlands
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The
Immune System and Autoimmune Diseases Linda
Aronson, PetShrink, (978)
838 0143; Fax 978 838 0216 www.petshrink.com Introduction
to the immune system The
immune system is designed to protect the body from disease causing
pathogens and other foreign substances. It is an amazingly complex
system, and we are probably only just beginning to appreciate its many
parts and functions. For
example, recent research has shown changes in the immune cells in human
patients suffering from severe mental illness.
It is hoped these changes can form the basis for a diagnostic
test for these illnesses and allow for earlier intervention.
In this paper I will merely hope to give an overview of the parts
of the system involved in preventing infection, and the ways in which
the system can fail. The body
has a number of lines of defense.
The skin is a wonderful barrier.
The gut-associated lymphoid tissue (GALT) is the biggest immune
organ in the body, and about 70% of the body’s immune system is to be
found in the intestinal lining. The
digestive tract must strive to exclude unwanted pathogens while allowing
nutrients to enter the body and coexisting with commensal (good)
bacteria that help digest food and make necessary enzymes and vitamins,
while preventing overgrowth by toxic bacteria and fungi.
Acid in the stomach kills many microorganisms, while the mucus
lining of the gut contains antibodies to neutralize others.
Enzymes, especially those in bile and saliva, detoxify some
pathogens while others break down food substances into their smallest
elemental units. Coordinated
waves keep food moving through the gut.
In the developed world the delicate balance of the gut is often
disrupted and inflammatory bowel disease is becoming increasingly common
in our dogs. In humans
there have been studies demonstrating that improved hygiene and the loss
of intestinal parasites which have coexisted for millennia may be
responsible and replacing them with benign parasites may be curative.
There may also be mutations in the genes that control innate
immune recognition, adaptive immunity and epithelial permeability all of
which may contribute to the inflammatory response as well as food
allergies. The respiratory
and genitourinary tracts are similarly protected by a combination of
mechanical and chemical barriers. The skin,
lungs and intestines (as well as circulating white blood cells) are
populated by specific peptides – small portions of protein - (e.g.
cathelicidins) that act as natural antibiotics.
They help to contain fast moving infections until the immune
system can mount a fully orchestrated attack.
While bacteria have been able to develop resistance to artificial
antibiotics, they have never been able to develop immunity to these
peptides. It is hoped that
boosting this natural defense system may provide a successful means of
combating antibiotic resistant infections such as MRSA (methicillin
resistant Staph. Aureus);
necrotizing fasciitis (the flesh eating bacteria); or toxic shock
syndrome. If the
physical barriers to infection fail, the next line of defense is
provided by the innate immune system, which identifies infectious agents
by their pattern or structure and provides an immediate but non specific
response (inflammation, release of chemicals to bring various immune
cells or which kill invading organisms).
If pathogens evade this system there is a final adaptive immune
system which is specific for particular pathogens and antigens, but
which takes several days to gear up initially to a new infectious
organism. However, once a
particular microbe has been encountered specific antibodies are formed
against it, and can be called into action on subsequent exposures.
Antigens are molecules that generate an antibody response.
Both innate and adaptive immune systems have humoral components found in
the body fluids – primarily blood and lymph, and cellular ones. The
complement system is the primary component of the innate humoral
response; it so called because it complements antibodies in killing
pathogens. A biochemical
cascade of over 20 different enzymes attacks the surface of microbes to
which antibodies have attached. As well as releasing chemicals that eat
the organism, the cascade also attracts other immune cells, increases
the permeability of blood vessels facilitating their access to the
organism, as well as marking it for destruction. The
cellular component consists of various types of white blood cells:
phagocytes (macrophages, neutrophils and dendritic cells), mast cells,
eosinophils, basal cells and natural killer (NK) cells.
Phagocytes engulf and digest smaller pathogens.
They circulate throughout the body, but are attracted by
substances released by the complement cascade. Neutrophils
usually represent the majority of white cells in the blood, while
macrophages are usually found in the tissues. They
also scavenge dead cells, and present cells to antibodies.
Dendritic cells are phagocytes in skin, nose, lungs and
gastrointestinal tract where they have contact with the external
environment. Mast cells are
found in connective tissues and mucous membranes and they regulate the
inflammatory response. Over-activity
results in allergic and anaphylactic reactions.
Basophils and eosinophils are also circulating in the blood
stream and their primary role is defense against parasites, although
they also have a role in allergies. NK cells destroy tumor cells and
those infected with viruses.
The
adaptive immune system allows for a stronger immune response and also
provides immunological memory so that an antigen that has already been
encountered will produce a faster and more focused response.
It is the adaptive immune system that must be able to tell self
from non-self. Lymphocytes are the cellular component of the adaptive
immune system. There are
two major types, B cells are formed in the bone marrow and are involved
in the humoral response. They
are also known as immunoglobulins – IgG, IgM, IgA, IgD and IgE. T
cells originating in the thymus produce the cell-mediated response
involving the lymph nodes, thymus, spleen, GALT, tonsils and mucus
secretion. Both types have
receptors that recognize specific targets.
The B-cell receptor recognizes whole pathogens.
T-cells only recognize small fragments of pathogens that have
been processed and presented by other (MHC) molecules.
There are two major types: killer T cells kill cells infected
with pathogens as well as those that are damaged or dysfunctional.
Each T cell recognizes a single antigen.
Helper T cells, having recognized the antigen, release chemicals
to stimulate and increase the activity of B cells, killer T cells and
macrophages, and regulate both innate and adaptive immune systems.
A third class of T cells, suppressor T cells dampen the immune
response if it becomes overactive or out of regulatory control. Activation
of the B and T cells causes them to reproduce and their progeny become
long-lived memory cells ready to mount an immune response to any
subsequent encounters with the pathogen.
Newborn puppies have not been exposed to pathogens and lack this
active memory. They have
however, received passive immunity from their dams.
A particular kind of antibody – IgG - is transported across the
placenta providing the neonate puppy with immunity to antigens
encountered by the dam. The
first milk, colostrum, also contains antibodies (all classes) against
primarily bacterial infections, as well as lymphocytic cytokines –
which are immune regulators; interleukins that control inflammatory
response; interferon which inhibits viral reproduction; and other
substances that support an effective immune response.
These large molecules can only cross the intestinal wall for the
first 24-48 hours so it is important that the puppy receives colostrum.
If the bitch has none, hyperimmune plasma can be tubed in during
this time slot to provide passive immunity.
The puppy does not make antibodies or memory cells in response to
these antibodies, and the immunity gradually wanes over the first weeks
of the puppy’s life, unfortunately persistence is highly variable.
Long term active immunity is obtained by activation of B and T
cells when they encounter an infection or artificially through
vaccination. Disorders
of immunity
The
immune system is a complex one that is both specific and adaptive to the
dog’s changing environment. Its
complexity unfortunately makes it susceptible to failure.
There are basically three potential problems.
In immunodeficiency one or more of the components are
inactive. Ability to
respond is reduced in the young and elderly.
Malnutrition, particularly the lack of sufficient protein, iron,
copper, zinc, selenium, Vitamins A, C, E, B6 or folic acid,
is one cause. Environmental
toxins, genetic or acquired diseases, and certain cancers can also
result in immunodeficiency. Hypersensitivity
is the result of an excessive response that results in damage of the
body’s own cells. There
are four classes. Anaphylactic
reactions are often associated with allergy and can range from mild to
fatal. They are caused by IgE released from mast cells and basophils.
Cytotoxic hypersensitivity results from IgG or IgM antibodies
attaching to the body’s own cells and marking them for destruction.
Type III is caused by the deposition of immune complexes of
antigens, compliment proteins and IgG and IgM antibodies in the tissues.
Type IV hypersensitivity includes many autoimmune and infectious
diseases as well as contact dermatitis and is mediated by T cells,
monocytes and macrophages. Autoimmune
reactions are a specific form of over-reactivity in which the immune
system fails to distinguish self from non-self resulting in it attacking
parts of its own body. Specialized cells in the bone marrow and thymus
normally eliminate any lymphocytes that present with self antigens.
Different
hormones can stimulate or suppress the immune system.
Estrogen hormones can stimulate both innate and adaptive immune
systems, which is why some autoimmune diseases are more common in
bitches and occur after she is sexually mature.
It appears that testosterone may suppress the immune system,
while progesterone prevents the bitch rejecting the fetuses as foreign,
but also dampens the general immune response.
Prolactin and growth hormone also affect the immune system in a
complex fashion. Declining
levels of hormones in older animals may contribute to a reduced immune
response in older animals. The
immune system regulates thyroid activity and vice versa.
Stress impairs immune reaction, while rest enhances it.
Malnourished fetuses and neonates will suffer a lifelong
impairment, while certain foods – especially essential fatty acids as
well as some other foods and herbs can stimulate it.
Drugs
can also be used to manipulate the immune system.
Immunosuppressive drugs are used to control autoimmune diseases
and to reduce inflammation as well as to prevent rejection of
transplanted organs. Glucocorticoid
drugs are the most potent anti-inflammatory drugs, but they have serious
side-effects. Other drugs,
such as azathioprine, are cytotoxic and suppress the immune response by
indiscriminately killing rapidly dividing cells such as activated T
cells, but also those in other organs causing toxic effects.
A third class of drug inhibits the signals that activate T cell
response, cyclosporine does this. Antibiotics enhance immune response,
but will not be considered here. Neither
will the various strategies employed by pathogens to elude the immune
response at all levels. Autoimmune
Diseases
At
this time we are only beginning to untangle the causes of these
diseases. In the majority
of cases there appears to be a genetic factor necessary, but disease
will not be seen without some external trigger.
Sometimes we can pinpoint this – a vaccine, drug, toxin or
illness (usually viral or bacterial) – but often the trigger is not
identified. Hormones and
stress are also triggers for disease.
Are autoimmune diseases more common now or are we better at
detecting them? The answer
is probably both. Certainly, we and our dogs live in an increasingly
artificial environment laden with chemicals; food is laced with
ingredients that are anything but natural.
I come across repeated instances of households where owners and
their animals have an assortment of different ailments that are all
autoimmune in nature. However,
veterinarians and owners are also more aware of the problem.
Over and over I hear that an unexplained problem is probably
autoimmune with no real idea of what disease is suspected.
Just because a problem responds to immunosuppressive drugs
doesn’t mean that it was the result of autoimmune disease. Certain
immune-suppressant viruses (retroviruses and parvoviruses) have been
implicated as causing bone marrow failure, the immune mediated blood
diseases (autoimmune hemolytic anemia – AIHA - and immune-mediated
thrombocytopenia – ITP), lymphoma, leukemia, dysregulating humoral and
cell-mediated immunity, liver and kidney failure, and autoimmune
endocrine disorders – thyroiditis, hypoadrenocorticism (Addison’s
disease) and diabetes. Viral
disease and recent vaccination with single or combined modified live
viruses are also triggers for immune-mediated blood disease, bone marrow
failure and organ dysfunction. The
killed rabies vaccine and bacterial leptospirosis vaccine more commonly
trigger immediate or delayed vaccinosis reactions.
The bacterial (Ehrlichia, Anaplasma, Rocky Mountain Spotted
Fever) Protozoal
(Babesia) and spirochetal (Lyme disease) tick borne diseases suppress
the host immune system and decrease the numbers of antibodies making the
animal susceptible to secondary infection, while inducing autoimmune
diseases of the blood (AIHA and ITP), gut (IBD), muscles (myositis), eye
(uveitis), joints (polyarthritis) and in the case of Lyme a protein
losing disease of the kidney -the latter two closely mimic systemic
lupus erythematosus (SLE). When the apparent autoimmune disease has been
addressed titers for the tick borne diseases are often found to be sky
high, as these organisms can adapt and survive within the body for years
or even permanently. Skin
“allergies” are also indicative of an immune system gone awry. Drugs
associated with exacerbating or triggering autoimmune disease include
potentiated sulfonamides (trimethoprim-sulfa and related antibiotics),
monthly heartworm drugs (especially those combined with flea
preventatives) and anticonvulsant drugs.
As stress and the need for drugs tend to go hand in hand
virtually any drug is capable of acting as a trigger in a susceptible
individual. Autoimmune
thyroiditis Hypothyroidism
is arguably the most common endocrine disease in dogs and in the
majority of cases it is autoimmune in nature. Because
the thyroid hormones regulate metabolic function in all the body’s
cells even suboptimal function can result in profound changes throughout
the body that can be missed – written off as puppy exuberance/ADD or
normal aging – or mistaken for some other disease.
By the time the classical presentation of obesity, lethargy,
heat-seeking and alopecia is achieved two-thirds of thyroid function or
more has been lost. Monitoring
thyroid function regularly through comprehensive thyroid panels is one
of the most important things we can do to ensure good health for our
dogs. Reduced thyroid
function results in depression of the immune response to other diseases.
It often accompanies other autoimmune disorders and any dog
diagnosed with autoimmune disease should have a thyroid panel run.
Supplementing the thyroid usually results in a better prognosis
for these diseases as well as reducing the need for other, often more
expensive or toxic, drugs. Early
signs are often behavioral in nature – increase in fear, aggression or
obsessive behaviors, as well as an inability to focus and learn in young
animals. Young animals,
unlike older dogs, often are uninterested in food, underweight and
hyperactive. Commonly seen
signs include: ____Excessive
shedding, patchy hair loss or “rat tail” Diagnosis
via a complete thyroid panel consisting minimally of serum levels of
total and free T3 (triiodothyronine) and T4 (thyroxine) preferably with
levels of T3 , T4 and thyroglobulin antibodies.
Because dogs
under 18 months, toy and giant breeds as well as sighthounds have
different thyroid requirements it is recommended that serum be sent to
Hemopet Diagnostics service for evaluation www.hemopet.org
If a dog has low or suboptimal thyroid function, treatment with
L-thyroxine twice daily at a dose of 0.1mg/12-15 lbs body weight should
resolve any of the above problems. Hypoadrenocorticism
(Addison’s Disease) See
separate article.
Autoimmune
hemolytic anemia (AIHA aka Immune mediated Hemolytic Anemia –IMHA)
Anemia per se is a clinical
sign not a disease, and is simply a decrease in the number of red blood
cells (RBCs) or the amount of hemoglobin, resulting in a decrease in the
oxygen-carrying capacity of the blood. Anemia can be caused by blood
loss, decreased production of new RBCs, or an increase in the rate of
their destruction - hemolytic anemia. Senescent RBCs acquire
markers on the cell surface that are recognized and are removed from
circulation usually by the spleen and/or liver.
Similarly markers appear on RBCs in cases of AIHA.
These markers can be true autoantibodies, as in primary AIHA, or
can be secondary to drugs (the immune stimulator and wormer levamisole,
certain antibiotics, and the anticonvulsant anti-arrhythmia drug
phenytoin have been implicated), infectious disease, cancer, blood
parasites, or heavy metals (lead, and zinc). AIHA
results when red cells are removed faster than they can be replaced. Antibodies
can be warm (usually IgG reactive at body temperature) or cold type
(usually IgM when body temperature drops below normal).
As well as being removed by spleen and liver, RBCs are destroyed
in the blood vessels when the immunoglobulins (usually IgG) activates
compliment. RBCs may also
clump as a result of bridges formed between cells usually by IgM.
Clinical signs of AIHA can
appear gradually or suddenly and relate to the lack of oxygen reaching
the tissues – collapse/weakness, lethargy, anorexia, exercise
intolerance and an increase in the heart and respiratory rates. Mucous
membranes (gums, eyelids, etc.) are usually pale and heart murmurs may
be heard. Vomiting and
diarrhea are not uncommon. Lymph
nodes are usually swollen. In
more severe cases a fever and "icterus" (jaundice) - a yellow
discoloration of the gums, eyes, and skin due to a buildup of bilirubin,
one of the products of hemoglobin breakdown – will be found.
Anemia is confirmed by complete blood count (CBC).
A Coombs test and clotting time tests may also be used to confirm
diagnosis although only about 60% of patients with AIHA have a positive
Coombs test. Palpation and
radiographs confirm enlargement of the spleen and liver.
In chronic cases the heart may be enlarged.
Anemia can be regenerative or non regenerative.
In the latter case, there is immune mediated destruction of RBC
precursors in the bone marrow. In severe cases blood transfusion with cross-matched packed red cells or whole blood and intravenous fluids may be necessary. Corticosteroids are usually the first drug given and are started at very high immunosuppressive doses, the dose is very slowly tapered over many weeks or months to a low maintenance dose. Some affected dogs have to be kept on low steroid doses for the rest of their lives and most are susceptible to relapse. Other immunosuppressive drugs such as azathioprine (Imuran) or cyclophosphamide (Cytoxin) may be added. If the drugs have failed to produce significant improvement after 4 to 6 weeks splenectomy - the surgical removal of the spleen - may be recommended. Immune-mediated
thrombocytopenia (ITP)
ITP is the destruction of
platelets also known as thrombocytes by the binding of antibodies to the
platelets’ surface leading to their premature removal from
circulation. ITP often
accompanies AIHA. Platelets
attach to cell walls when they are damaged and help produce a clot to
prevent blood loss either within the body or through the skin and other
external surfaces. Generally
we are unaware of all the minor breaches that occur all the time.
If platelet numbers drop sufficiently low (<40,000)
spontaneous hemorrhaging can occur usually into the skin, g/i tract,
respiratory or urinary systems. Typically
presentation results from hemorrhage into the skin (petechiation)
causing small or large blood blisters, excessive bleeding from minor
traumas, vomiting, urinating or defecating blood, lethargy, weakness or
collapse – although these last three signs are more likely if there is
accompanying AIHA. Other
causes of clotting disorder - rat poison, hemophilia, von Willebrand’s
disease, bladder and prostate infection, cancer or intestinal parasites
- should be ruled out. CBC,
Coombs test, vWF and clotting tests are performed and bone marrow
samples may also be taken. Drug
treatment is usually the same as for AIHA.
A single injection of vincristine may be given in extreme cases
as it will produce a large increase in platelet numbers three days
later. Transfusion of whole
blood or platelet rich plasma may also be indicated.
Once platelet counts are normal ovariohysterectomy (spaying) is
recommended in intact bitches to prevent hemorrhage during estrous.
Due to the genetic component in autoimmune diseases it is
strongly recommended that affected dogs should not be used in a breeding
program. Systemic
lupus erythematosus (SLE)
SLE also often
accompanies/causes AIHA and/or ITP.
It is a multi-systemic autoimmune disease often simply referred
to as lupus. It is the result of autoantibodies to non-organ specific
nuclear and cytoplasmic antigens as well as cell and organ specific
antigens. The resulting
immune complexes are deposited in multiple locations throughout the
body, but most commonly the glomerular membranes in the kidney, synovial
membranes in joints, the skin, mucous membranes, blood and brain.
Complement is activated leading to inflammation as well as direct
toxic damage to surrounding structures.
Clinical signs depend upon where the immune complexes are located
and the specificity of the autoantibodies.
The signs of SLE may be acute (sudden onset) or chronic but are
almost always cyclic – wax and wane. A fluctuating fever that does not
respond to antibiotics is often seen.
Joints may be swollen and painful resulting in a stiff gait or
shifting lameness. Symmetrical
or local skin lesions with redness, scaling, ulceration and loss of hair
are also common as are ulcerative lesions in the mouth and junctions
between haired skin and mucous membranes.
Glomerulonephritis results from leaky membranes in the glomeruli
– filtration units of the kidney – leading to poor filtration and
loss of protein into the urine. Heart
murmurs and arrhythmias and pleural friction rubs are due to
inflammation of heart muscle and the sacs around heart and lungs.
Muscle wasting and inflammation, enlarged lymph nodes and spleen,
low white cell counts, depression, seizures and changed mentation round
out the possible symptoms.
While a CBC and antinuclear
antibody test (ANA) should be run, along with appropriate diagnostic
tests for specific systems affected diagnosis is based on the number of
major and minor signs of SLE present.
A false positive ANA can result from a number of infectious
diseases such as some of the tick borne diseases, which also present
with polyarthritis. While
immunosuppressant drug therapy is the cornerstone of treatment of SLE,
treatment is also directed at the particular systems affected by the
disease where possible. Prognosis
is guarded especially where kidney disease is advanced or there is
secondary infection (pyelonephritis), septic arthritis in the joints or
septicemia in the blood. Autoimmune
diseases of the skin
These
are a group of autoimmune diseases that are definitively diagnosed by
skin biopsy and/or immunofluorescent staining, and which generally
respond quite well to corticosteroids and/or other immunosuppressants.
There are four members of the pemphigus group characterized by
varying degrees of ulceration, crusting, pustules and vesicles.
Pemphigus foliaceus is the most common and usually involves the
head, ears and footpads, although it can become generalized.
It rarely affects mucous membranes, but may affect nail beds.
(When it does it may be a case of mistaken identity and actually
be symmetrical lupoid onychodystrophy – SLO – also thought to be an
autoimmune disease and only affecting the nails.
Definitive diagnosis requires amputation of the final toe bone
(P3) holding the claw, and many owners are unwilling to do this.)
Secondary skin infections are common.
Pemphigus erythematosus is most likely a milder form of P.
foliaceus and is localized to head, face and footpads especially on the
nose where it is aggravated by ultraviolet light.
Pemphigus vulgaris is the most severe form causing more severe
lesions and also affecting the mouth, mucous membranes and mucocutaneous
junctions, axillae (arm pits) and groin.
The blisters are thin, fragile, and rupture easily, while the
skin lesions are usually red, weeping, ulcerated plaques.
Pressure on the skin around a lesion causes new or extended
lesions to form. Dogs are
often itchy and painful, and may be anorexic, depressed, feverish and
develop secondary bacterial infection at the lesions.
Pemphigus vegetans may be a benign form of P. vulgaris and
consists of oozing pustules and thick vegetative lesions, but no
systemic illness nor involvement of the mouth.
P. foliaceus and vulgaris may require life long treatment with
immunosuppressants, while P vegetans and erythematosus may need oral
corticosteroids or respond to topical corticosteroids.
Discoid lupus erythematosus
may be a benign form of SLE and causes dermatitis of the face - usually
over the bridge of the nose. Lesions are similar to and often mistaken
for nasal solar dermatitis (also known as collie nose) and pemphigus
erythematosus. Tattooing
the area may prevent sunburn. Vogt-Koyanagi-Harada-like
syndrome (VKH) is extremely rare and may be autoimmune in origin.
It causes depigmentation of the nose, lips, eyelids, footpads,
and anus and they fade to pink or white, and there is an accompanying
acute uveitis (inflammation of the eyes). Early
treatment may prevent blindness, but the pigment loss is usually
permanent. Polyarthritis
Immune-mediated
polyarthritis can be seen in SLE as above or as an independent finding.
There are several different diseases included under this umbrella term,
but the major signs for all of them include high fever, joint pain and
swelling, and a lameness that seems to shift from leg to leg. Lymph
nodes may be enlarged. Rheumatoid arthritis (RA) is the most severe form
and X-rays of the joints will show erosion of cartilage and eventually
bone. Rheumatoid factor can
usually be found in the blood. X-rays
in the milder non-erosive forms will appear normal.
Other blood work may be normal or show abnormalities and what
changes there are will not be consistent.
In uncomplicated immune-mediated polyarthropathies, clinical
remission can be achieved with corticosteroids in about half the cases.
For the rest, azathioprine or cyclosporine is usually effective, and
remission can be maintained with corticosteroids.
With the exception of rheumatoid arthritis, the prognosis is
generally good. Muscle related autoimmune
diseases Myositis can be generalized
– polymyositis (affecting skeletal muscles of limbs and jaw;
dermatomyositis also has skin lesions) or focal affecting either the
masticatory muscles (temporalis muscle over the head and jaw muscles) or
extraocular muscles around the eye.
The muscles affected are usually stiff and painful and may be
acutely swollen, but they atrophy over time. Autoantibodies are directed
against muscle fibers. Polymyositis
may also be caused by infectious diseases, certain cancers and some
drugs, so muscle biopsy is needed to confirm an autoimmune etiology.
Focal myositis is often diagnosed by response to
immunosuppressive drugs. Corticosteroids
should produce full remission provided there has been no fibrosis of the
muscles prior to treatment. One
potential complication of polymyositis is megaesophagus, an enlargement
of the entrance to the esophagus which prevents closing the trachea when
swallowing food. This can
result in food entering the trachea and causing infection (aspiration
pneumonia). Myasthenia gravis may
rarely be congenital but is usually an autoimmune disease resulting from
autoantibodies attaching to the acetylcholine receptors that transmit
nerve signals to muscles causing them to contract.
The receptors are destroyed and often the surrounding cell
membrane as well. Dogs may present with focal weakness of muscles in the
esophagus, pharynx or around the eye or with generalized muscle weakness
so the dog cannot support its own weight.
Megaesophagus and aspiration pneumonia are common.
Serum acetylcholine antibody receptor titer is diagnostic as is
response to the anticholinesterase drug edrophonium (which prolongs the
action of acetylcholine in the neuromuscular junctions).
Treatment is with a related more long acting drug called
pyridostigmine. Prednisone
is usually given at immunosuppressive doses, but it may initially make
the weakness worse. Other In humans type 1 (insulin
dependent) diabetes mellitus (DM) is an inflammatory autoimmune disease
resulting in destruction of insulin producing beta cells in the islets
of Langerhans. Autoantibodies
to insulin have been found in the dog suggesting that DM is
predominantly an autoimmune disease in the dog.
Pancreatitis may also be a possible cause.
The number of cases of DM appears to have increased dramatically
since kibbled foods became the predominant form of canine nutrition, and
as these must be 60% carbohydrate as opposed to about 5% carbohydrate in
the diet of most wild canids, metabolic disease may also be responsible
or at least a contributing factor.
Kerratoconjunctivitis sicca (KCS) commonly known as dry eye
results from cessation of tear production and responds to the
cyclosporine suggesting an immune mediated etiology. Vitiligo
may represent an autoimmune destruction of the cells that produce the
pigment melanin. In
time it is likely other autoimmune diseases will be added to the list.
A grateful THANK YOU to Linda Aronson,DVM for the use of this article.
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