PEMPHIGUS : AUTOIMMUNE  DISEASE (AID) IN DOGS

PEMPHIGUS : AUTOIMMUNE  DISEASE (AID) IN DOGS

The term “autoimmune disease” covers a broad variety of disorders in dogs that affect the immune system.A dog’s immune system is a network of white blood cells, antibodies, and other defenses in the body that fight off infections and foreign substances, including bacteria and viruses. Canine autoimmune diseases cause the immune system to attack the body’s own cells and tissue. An autoimmune disorder can be life-threatening to dogs depending on which organ or tissue the immune system rejects. There are many types of autoimmune diseases in dogs with various symptoms. Treatment depends on the kind of autoimmune disorder.

Our bodies have an immune system that protects us from foreign invaders that can cause disease and infection. If you have an autoimmune disease, however, your immune system attacks itself by mistake, causing serious illness. The immune cells fail to distinguish the body’s normal healthy cells from foreign cells, and thus try to destroy the normal tissues. The cause of this “mistake” is not well understood. Autoimmune disease can affect a single system or multiple body systems. Autoimmune diseases can affect skin, connective tissues, nerves, muscles, the endocrine system (the system that controls hormones and other chemicals), red blood cells, and the digestive system. Dogs and cats with autoimmune diseases should not be vaccinated except under certain circumstances as advised by your veterinarian .

What causes autoimmune disease?

The cause or causes of autoimmune disease are not fully understood, although some theorize that genetics and/or environmental pollutants play a role. Ultraviolet (UV) exposure is thought to be a predisposing or “triggering” cause of autoimmune skin diseases in some dogs. Certain drugs have also been reported as potential triggers for pemphigus foliaceus, a common form of autoimmune skin disease in dogs and cats. Early recognition is extremely important. Left untreated, the complications of autoimmune disease are serious and multiple system involvement is common. This can make diagnosis and treatment very challenging and complicated.

Types of Canine Autoimmune Diseases

Autoimmune skin diseases are relatively rare in dogs. Some of the more common forms of autoimmune skin disease include:

The most common autoimmune diseases in dogs are:

• Immune-Mediated Polyarthritis (joint inflammation)
• Immune-Mediated Thrombocytopenia (platelet destruction)
• Keratoconjunctivitis Sicca (dry eye)
• Inflammatory brain disease (for toy breed dogs in particular)
• Pemphigus Foliaceus (a skin disease)

Common Autoimmune Diseases In Dogs

Here are brief descriptions of common autoimmune diseases in dogs.

1. Hypothyroidism

Most canine hypothyroidism is the result of an autoimmune process known as autoimmune thyroiditis. This is when your dog’s immune system develops antibodies against the cells in his own thyroid gland. As the cells are attacked and destroyed, the remaining cells must work harder to take over. It’s not until the gland is 75% destroyed, and can’t produce enough thyroid hormone, that your dog begins to show symptoms of thyroid issues.

The Merck Veterinary Manual states that 95% of the cases of canine hypothyroidism are because of immune-mediated destruction of the thyroid gland and not iodine deficiencies. That’s why it’s important to determine the cause before giving iodine or other supplements.

In addition to the more general autoimmune disease signs listed earlier, you may also notice:

• Thickening of the skin
• Obesity and weight gain without increasing food or appetite
• Cold and exercise intolerance
• Mental dullness

2. Lupus

There are 2 kinds of lupus

1, Systemic Lupus Erythematosus (SLE) is rare and can be fatal. Your dog’s immune system attacks the skin, blood, nervous system, and major organs. SLE can be fatal to dogs.

Symptoms vary and can duplicate other diseases. Here are the most common ones:

• Fever
• Anemia
• Swollen lymph nodes
• Seizures
• Lethargy, muscle pain and stiffness
• Sores in the mouth
• Hair loss and skin lesions
• Lameness that shifts between legs

2. Discoid Lupus Erythematosus (DLE) is more common and only affects your dog’s skin. Here are some signs:

• Sores, ulcers or scarring
• Pale skin on the nose
• Bacterial infections
• Itching and scratching
• Redness on the face nose and lips
• Skin that’s flaky or scaly

3. Immune-Mediated Polyarthritis (IMPA)

Immune-mediated polyarthritis appears when the immune system attacks the joints. It causes pain, swelling and affects your dog’s ability to walk. It can exist on its own or alongside SLE … or as a symptom of an autoimmune disease throughout your dog’s body.

This is what you’ll notice in your dog:

•  Fever
• Joint swelling and/or pain
• Lethargy due to discomfort
• Lameness that shifts from leg to leg
• Whining or yelping when moving or being touched
• Enlarged lymph nodes

4. Inflammatory Bowel Disease (IBD)

When your dog’s immune system overreacts to bacteria in the intestines, it causes inflammation and gastrointestinal symptoms that lead to inflammatory bowel disease. IBD is most often seen once dogs reach middle age, which varies by breed.

Here are symptoms you’ll see:

• Vomiting
• Diarrhea
• Blood in stool
• Bloating and gas
• Gurgling in the abdomen
• Weight loss
• Vomiting
• Discomfort in abdomen
• Depression and solitude
• Changes in coat texture

5. Immune-Mediated Hemolytic Anemia (IMHA)

Immune-mediated hemolytic anemia can be a primary disease meaning the cause isn’t readily known. Or it can be a secondary disease when the immune system’s antibodies destroy its own red blood cells. This can happen when there’s an existing condition like cancer, an infection, or the influence of drugs or toxins. Because a major role of red blood cells is to transport oxygen through the body, when there’s anemia, there’s a shortage, all parts of the body are starved for oxygen. A severe loss of red blood cells can be life-threatening.

These are signs of hemolytic anemia in your dog:

• Pale or white gums
• Weakness, lethargy, fatigue
• Depression and desire to sleep
• Lack of energy or interest
• Decreased appetite
• Dizziness
• Extremities are cold
• Difficulty breathing and shortness of breath
• Irregular heartbeat
• Jaundice

6. Immune-Mediated Thrombocytopenia (IMT)

Like IMHA, immune-mediated thrombocytopenia can appear as a primary or secondary disease. Instead of red blood cells, the immune system destroys its platelets. Platelets help form blood clots to stop bleeding. When large numbers are destroyed, you will probably see pinpoint bleeding in the skin or gums or bleeding from your dog’s nose. This appears in female dogs more than in males.

Here are signs of thrombocytopenia in your dog:

• Bruising of skin or gums
• Nosebleeds
• Blood in urine and stool
• Weakness and lethargy

7. Diabetes

Type 1 diabetes mellitus is an autoimmune disease. It happens when the pancreas stops making insulin. The cause is when the immune system attacks the pancreas and destroys the insulin-producing cells.

Here are signs of diabetes in your dog:

• Frequent urination – your diabetic dog will drink and pee a lot
• Hunger as your dog’s cells demand glucose
• Weight loss – your dog will burn off tissue to produce glucose, and he’ll lose weight
• Vomiting – especially if your dog has pancreatitis
• Tired, lethargic or weak

This is a disease where antibodies attack your dog’s thyroid that is responsible for controlling the metabolism of the body. When it’s under attack, the thyroid gland doesn’t produce enough hormone. That can lead to other diseases.

The symptoms are extensive and can include:

• Muscle fatigue and weakness
• Slow heart rate
• Loss of interest in activity, lethargy
• Obesity
• Diarrhea
• Constipation
• Vomiting
• Hair loss and dandruff
• Thinning skin
• Darker skin pigmentation
• Dry eye
• Cold intolerance

8. Myasthenia Gravis

This condition occurs when antibodies of the immune system attack the neurotransmitters that control your dog’s muscle function.

You’ll notice these signs:

• Muscle weakness
• Lack of muscle control
• Fatigue
• Loss of interest in exercise or play
• Difficulty swallowing
• Regurgitating food, not to be confused with vomiting

9. Rheumatoid Arthritis

This is chronic inflammation of the lining of the joints, leading to pain and swelling. It happens when the immune system attacks the immunoglobulin G that regulates the circulatory system.

Here are signs you’ll see:

• Swelling of joints
• Lameness and difficulty walking
• Elevated body temperature
• Limited or restricted joint movement
• Inability to move joints
• Dislocated joints
• A sound of cracking or grating when joints are moved

10. Addison’s Disease (Hypoadrenocorticism)

Addison’s disease and hypoadrenocorticism are one and the same disease. It occurs when your dog’s adrenal glands are attacked by the immune system  and can’t produce enough cortisol and aldosterone. These 2 hormones regulate many important bodily functions. Cortisol is a stress hormone that also helps control metabolism, blood pressure and sugar levels. Aldosterone regulates sodium and potassium levels to control blood pressure. Anything that damages the adrenal glands can lead to Addison’s disease.

Common symptoms of Addison’s disease in dogs include:

• Loss of appetite and weight loss
• Depression and lethargy
• Diarrhea
• Vomiting
• Blood in stool
• Hair loss
• Hypoglycemia
• Low body temperature
• Irregular heart rate
• Darkened skin pigment

11. Bullous Autoimmune Skin Diseases

These are autoimmune diseases that attack your dog’s skin, especially the connections between skin cells. There are three causes.

• Endogenous pemphigus can be due to genetic or breed disposition, or an immune system defect.
• Exogenous pemphigus is from an outside influence that sets off the immune system.
• Idiopathic pemphigus has no known cause for the immune system attacking the cellular connections of the skin.

And within those, there are 5 varieties of pemphigus in dogs.

• Pemphigus Vulgaris – This is a rare disease, but very serious. Secreting ulcers form around orifices. They form at any skin level but usually deeper in the skin.
• Pemphigus Foliaceus – This is more superficial with pustules just under the surface of the skin, usually on the head and nose, along with peeling foot pads.
• Pemphigus Vegetans – You’ll see postules and papillomas that look like small warts in the groin area.
• Bullous Pemphigoid – Its ulcers and blisters are similar to those of pemphigus vulgaris but they form deep in the skin. It is less severe.
• Pemphigus Erythematosus – This is usually found around the eyes, ears and bridge of the nose, with secreting sores and crusting.

Common symptoms seen in these conditions are:

• Balding and hair loss
• Skin ulcers
• Open sores or blisters
• Scabbing of the skin

 

Pemphigus complex

Pemphigus is a group of five autoimmune skin diseases characterized by vesicles and bullae (large and small “blisters”) in the mouth and at mucocutaneous junctions (the junction between skin and mucosal tissues). Commonly affected areas include the eyelids, lips, nostrils, and anus.

Pemphigus Foliaceus (PF) – The term means “leaf-like pemphigus” and this is the most common immune-mediated skin disease of dogs and cats. Pemphigus foliaceus is rarely found in the mouth or at mucocutaneous junctions. In this form of pemphigus, the patient develops crusts (scabs) and ulcers around the eyes, ears, footpads, groin and bridge of the nose. Breeds more commonly affected included the Chow chow, akita, cocker spaniel, Labrador retriever, dachshund, English bulldog, Finnish spitz, and schipperke. Pemphigus foliaceus usually appears suddenly without a recognized cause. In some cases, however, it may be drug-induced or can be the result of years of chronic skin disease.

Pemphigus vulgaris (PV) – The term means “common pemphigus” and it is the most frequent form of pemphigus in humans. Fluid filled blisters called “vesicles” form in and around the mouth, eyelids, lips, nostrils, anus, prepuce or vulva. These vesicles rupture easily, creating painful ulcers. This condition is rare in dogs.

Pemphigus erythematosus (PE) – The term means “red and inflamed pemphigus” and its most common symptom is redness, crusting, scales and hair loss on the nose. Exposure to ultraviolet light worsens this form of pemphigus. Breed predispositions include the German shepherd dog, collie, and Shetland sheepdog.

Pemphigus vegetans – This form is typified by thick and irregular vegetative lesions or lumps associated with chronic “oozing” and pustules. It is believed to be a more benign form of pemphigus vulgaris. This condition is rare in dogs.

Paraneoplastic pemphigus (PNP) – The least common (considered extremely rare) and most severe type of pemphigus. This condition is associated with the presence of an underlying malignant tumor.

Bullous Pemphigoid

Bullous pemphigoid may sound like a form of pemphigus, but it is actually a different type of autoimmune skin disease. Bullous is the medical term for a large thin-walled sac filled with clear fluid. Usually, the skin is very itchy and large red welts and hives often appear before or during the formation of blisters. Vesicles and ulcers may be found in the mouth, at mucocutaneous junctions, and in the axillae (armpits) and groin. Evaluation of the vesicles is critical to the diagnosis. Because vesicles rupture quickly after formation, the dog must often be hospitalized and examined every two hours until adequate biopsies can be obtained. Bullous pemphigoid resolves spontaneously in many cases. It is considered rare in dogs and cats.

Systemic Lupus Erythematosus

The classic example of a multi-systemic autoimmune disease is systemic lupus erythematosus (SLE), commonly referred to as lupus. Lupus is often called the “great imitator” because it can mimic almost any other disease state. The signs of SLE may be acute (sudden onset) or chronic, and usually they wax and wane. A fluctuating fever that does not respond to antibiotics is one of the classic clinical signs of SLE. Stiffness in the legs or shifting-leg lameness is also frequently reported with SLE. Other clinical signs may include blood abnormalities such as hemolytic anemia, thrombocytopenia (low platelet numbers), leukopenia (a low white blood count), and symmetrical dermatitis, especially over the bridge of the nose (often called a “butterfly lesion”). SLE is considered a more common cause of autoimmune skin disease in dogs and rare in cats. Dogs or cats with SLE should not be vaccinated unless first discussed with your veterinarian. Breeds reported in the literature include Nova Scotia duck tolling retriever, Shetland sheepdog, collie, German shepherd dog, Old English sheepdog, Afghan hound, beagle, Irish setter, and poodle.

Discoid Lupus Erythematosus 

Discoid lupus erythematosus (DLE) is another autoimmune skin disease seen in dogs and rarely in cats. Another common name for this condition is “Collie nose,” although it can appear in many breeds. DLE is seen more commonly in Collies, Shetland sheep dogs, German shepherds, and Siberian huskies. Exposure to sunlight and UV radiation is thought to be a potential cause or trigger. In most cases, affected dogs lose the pigmentation around the nose, although the skin around the lips, eyes, ears and genitals may be also affected. DLE can transform the surface of the nose from its normal “cobblestone” texture to smooth, flat and shiny. Ulcerated sores may occur. Some dogs find the disease irritating while others do not seem affected by it. DLE may be a non-systemic, less-serious type of systemic lupus erythematosus (SLE). It is considered a relatively benign autoimmune skin disease.

How is autoimmune skin disease diagnosed?

To definitively diagnose autoimmune skin disease, a biopsy of the affected skin is needed. Depending on the location, a skin biopsy may be performed with a local anesthetic. However, if the affected area involves the nose or face, or if the patient is anxious, sedation or general anesthesia may be required. A small round block of skin is removed with an instrument called a punch biopsy. This tissue sample is then sent to a veterinary pathologist to determine the diagnosis.

How is autoimmune skin disease treated?

The general treatment for autoimmune skin disease is immunosuppression. This means that your dog will receive drugs to reduce or attenuate the reaction of the immune system that is causing the disease. For many dogs, treatment with prednisone or dexamethasone will be sufficient. Other dogs require stronger immunosuppressant medications such as azathioprine, chlorambucil or oral cyclosporine. If secondary bacterial infections are present, antibiotics and medicated baths will be used. Your veterinarian will determine the optimal treatment plan for your dog’s condition.

What is the prognosis for autoimmune skin disease?

The prognosis for autoimmune skin disease depends on your dog’s specific diagnosis and the severity of symptoms.

In general, this is a potentially life-threatening condition requiring extensive diagnostic tests and treatments. Autoimmune disease is rarely curable, but is often controllable with the appropriate medication.

 

What is pemphigus?

Pemphigus is an autoimmune skin disease, in which the body’s immune system attacks the connections between its own skin cells. Pemphigus foliaceus (PF) is an autoimmune disease, with IgG and occasionally IgM antibodies targeting intercellular (transmembrane) proteins that hold the epidermal cells together. While in people this targeted protein is usually desmoglein-1, this is only the target protein in a minority of dogs.¹ In dogs the target is another protein, desmocollin-.The target protein(s) in cats has not been identified.PF usually presents in one of two forms, a mucocutaneous and encrusted pustular disease starting on the nasal planum, periocularly and the foot pads, and a generalized and encrusted (often pruritic) dermatosis.³ This latter form is more common in Chow Chows, Retrievers, Setters, and cats, and often associated with systemic signs such as fever or lethargy. Pruritus is variable, but is frequently noted in cats. Crusts may also occur around the nipples, particularly in cats, and can appear on the pinna, mimicking squamous cell carcinoma in white cats. Cats will also often present with paronychia (crusts and inflammation of the claw bed). Certain dog breeds appear at risk, such as Chow Chows, Bearded Collies, Schipperkes, Akita, and others.Histopathology of PF reveals subcorneal pustules filled with neutrophils (sometimes eosinophils) and acantholytic cells.

Drug-related pemphigus (RxP) Antibiotics, particularly trimethoprim-sulfa are the most common drugs reported causing this condition in small animals.

A topical anti-flea product containing metaflumizone and amitraz (now off the US market) has been documented as causing drug-related PF.¹⁴ More recently, another topical anti-flea medication, containing fipronil, amitraz and S-methoprene, has been implicated in causing PF.

Pemphigus vulgaris (PV) is a rare disease reported in both dogs and cats – the author sees a case about once every 5 years! As in people, IgG antibodies to desmoglein 3. German Shepherd dogs and Collies may be at risk. Clinical signs are mucocutaneous and mucosal ulcers; there may be a nasal planum/muzzle variant as well. Histopathology shows a suprabasal cell layer cleft with occasional acantholytic and inflammatory cells.

Paraneoplastic pemphigus (PNP) is another rare skin disease – only three dogs and one cat are reported in the literature.^17,19,22,22a As its name implies, the disease is secondary to a neoplastic, usually malignant, condition. Clinically the disease resembles PV.

What causes pemphigus?

There are three possible causes of pemphigus: endogenous (internal), exogenous (external) and idiopathic (unexplained).Endogenous cases of pemphigus are caused by some factor within the dog. These factors may include the dog’s breed or a genetic predisposition. Some dogs have defects in their immune function, making their immune system more likely to mount an attack against normal cells. Pemphigus may also be triggered by an underlying medical condition, such as chronic skin allergies or cancer.

Viral infections and ultraviolet (UV) light exposure can trigger inflammation in the skin, which can make a dog more likely to develop an autoimmune reaction such as pemphigus.

Exogenous causes of pemphigus include factors outside of the dog that can trigger an overactive immune response. Possible exogenous causes of pemphigus include anything that can trigger unusual inflammation. Viral infections and ultraviolet (UV) light exposure can trigger inflammation in the skin, which can make a dog more likely to develop an autoimmune reaction such as pemphigus. Drug reactions can also trigger pemphigus, either as a short-term allergic reaction to the drug itself (which will resolve once the drug leaves the system) or by creating lasting changes in the immune system of predisposed patients.Many cases of pemphigus are idiopathic in nature. Idiopathic means that no cause can be found, despite extensive testing. As frustrating as it may be for veterinarians and pet owners, these cases “just happen” and we do not know why.

What are the signs of pemphigus?

There are multiple types of pemphigus, and these different types often vary in their clinical appearance. The three most common types of pemphigus are pemphigus foliaceus, pemphigus vulgaris, and pemphigus erythematosus.

Pemphigus Foliaceus – Pemphigus foliaceus is the most common autoimmune skin disease in dogs and cats. It is often observed in middle-aged and older patients. Pemphigus foliaceus typically causes hair loss, scabs, and ulcers (open sores) around the head, face and ears. These lesions may become more widespread over time, covering other parts of the body. Pemphigus foliaceus is most commonly seen in Chow Chows, Akitas, Cocker Spaniels, Labrador Retrievers, Dachshunds, and English Bulldogs, though other breeds may also develop this condition.

Pemphigus Erythematosus – This form of pemphigus is similar in appearance to pemphigus foliaceus, although cases are often milder in appearance. Predisposed breeds include German Shepherds, Collies, and Shetland Sheepdogs.

Pemphigus Vulgaris  – This form of pemphigus attacks the deepest layers of the epidermis, making it the most severe type of pemphigus. Pemphigus vulgaris causes the formation of fluid-filled blisters, known as vesicles. These vesicles often rupture, leaving painful ulcerative lesions. Lesions often are seen at the edges of the lips and eyes, though they often will spread to other areas of the body over time.

How is pemphigus diagnosed?

The diagnosis of pemphigus requires a skin biopsy. Your veterinarian will use a biopsy punch to remove a small, circular plug of skin from a skin lesion. Depending on your pet’s temperament and the site of his lesions, this procedure may be performed with the aid of a local anesthetic injection or under general sedation/anesthesia.

“The diagnosis of pemphigus requires a skin biopsy.”

Once the skin biopsy sample has been removed, the biopsy site will be closed with sutures. Depending on the type of suture used, your veterinarian may have you return at a later date to have sutures removed. If your veterinarian used dissolving sutures, the sutures will dissolve on their own in the coming weeks.

After removal, the skin sample will be sent to a pathologist for analysis. By processing the skin sample and examining it under a microscope, the pathologist will be able to determine whether your dog has pemphigus.

How is pemphigus treated?

Pemphigus is an autoimmune disease. Therefore, treatment requires suppression of the immune system. Your pet will be treated with corticosteroids (such as prednisone) or other immunosuppressive drugs, such as azathioprine, chlorambucil, or cyclosporine.

Patients will require long term, sometimes lifelong, therapy to control signs of pemphigus. In addition, frequent rechecks will be needed to monitor the response to treatment and also to ensure that the patient is not developing negative side effects from medications. The goal is to use the lowest effective dose of medication to maintain remission of clinical signs.

What is my dog’s prognosis?

The prognosis for pemphigus varies depending on the type of pemphigus that is present.

Pemphigus vulgaris (PV) is a serious condition with a poor prognosis. Despite therapy, this disease is often fatal, due to its widespread effects on the skin. Fortunately, PV is far less common than other variants of pemphigus.

Pemphigus erythematosus (PE), in contrast, carries a good prognosis. While the skin lesions may be uncomfortable and unattractive, they rarely affect the dog’s overall health. Dogs with PE usually respond very well to treatment.

Pemphigus foliaceus (PF), the most common form of pemphigus, also carries a relatively good prognosis, though the individual response to treatment can vary. Some dogs with PF will achieve rapid control of clinical signs with medication and then be able to be gradually weaned off medication completely. Many dogs respond well, but require lifelong therapy. Unfortunately, some cases may be resistant to treatment and the prognosis in these cases is guarded.

12. Periodontal disease

Periodontal disease is inflammation that affects the teeth-supporting structures of your dog’s mouth. This is the major cause of tooth loss. It occurs when your dog’s immune system attacks its own tissues due to ongoing chronic inflammation. Several studies have concluded that autoimmunity plays a role in periodontal disease.

Causes of Autoimmune Diseases In Dogs

These influences can lead to autoimmune diseases in dogs:

1. Leaky Gut Syndrome

Factors like poor diet, toxins, overuse of pharmaceuticals, and stress can lead to inflammation that causes leaky gut in dogs. Your dog’s gut lining usually has “tight junctions” that prevent foreign substances from getting into the bloodstream. But when leaky gut develops, the gut lining becomes more permeable and allows toxins, allergens, bacteria and yeast into the bloodstream. Leaky gut can lead to many chronic diseases, such as arthritis, allergies, digestive issues, thyroid and other organ disorders. And several studies show that a leaky gut allows environmental factors to enter the body and trigger autoimmune disease .

2. Environment

Environmental factors like exposure to chemicals and toxins. 2014 research by Corsini et al found that heavy metals, PCBs, perfluorinated compounds (PFCs or PFOA) can affect antibody production and lead to immunosuppression . The study concluded: “Dysregulation(s) of immune system homeostasis can lead to adverse changes in immune functions, increasing the susceptibility to infections and cancer, as well as favoring the development of autoimmune diseases.”

In other words, environmental toxins can cause dysfunction that leads to improper cell destruction and autoimmune diseases.

3. Other Possible Factors

There’s conflicting research about whether there’s a link between vaccines and autoimmune disease in dogs.

In a 2017 paper, Laurel Gershwin DVM at UC Davis reviewed many different adverse effects of vaccination in dogs, including the potential for autoimmune disease.

Gershwin stated, “The notion that vaccination causes autoimmunity is almost certainly false. However, it is likely that a combination of genetics, environmental factors, and overstimulation of the immune system (which can occur as a result of overvaccination) contribute to the 1development of many autoimmune diseases.”

So the author denied a direct link … but did acknowledge that over-vaccination could possibly be a factor in autoimmune disease. But Gershwin’s review didn’t include a 1999 study at Purdue University titled Vaccine-Induced Autoimmunity In The Dog .Researchers Hogenesch H, Azcona-Olivera J, Scott-Moncrieff C, et al found that vaccinated dogs developed autoantibodies to many of their own biochemicals … including fibronectin, laminin, DNA, albumin, cytochrome C, cardiolipin, and collagen. The researchers believed this might be due to bovine serum and cell culture components in vaccines. Adjuvants in vaccines caused these bovine components to stimulate the dogs’ immune response and induce antibodies that cross-react with conserved canine antigens.”

Can Antibiotics Lead to Autoimmune Disease?

There’s no question that antibiotics can affect your dog’s immune system by harming beneficial bacteria in the gut. Designed to kill bacteria, antibiotics affect both good and bad bugs. Since 90% of the immune system is in the gut, this can disrupt the microbial balance that helps your dog resist disease. But it’s not clear whether this can lead to autoimmune disease.

A 2020 paper at the Cleveland Clinic and KU Leuven in Belgium, explored whether antibiotics may contribute to autoimmune disease using type 1 diabetes and IBD as two key examples. Results were mixed. They did find “some data suggest that widespread use of antibiotics may facilitate autoimmunity through gut dysbiosis,”  … but added, “there are also data to suggest antibiotics may hold the potential to improve disease activity.”

The study also mentioned that preclinical trials showed promising results for fecal microbiota transplants in treating autoimmune diseases, along with probiotic and prebiotic therapy.

Can You Avoid Autoimmune Disease In Dogs?

You can help prevent the development of autoimmune diseases in your dog by giving him good nutrition and reducing his exposure to toxins.So the soundest approach to avoiding autoimmune disease is to keep your dog in the best health you can, by feeding a healthy, fresh diet, minimizing toxins in his environment, and supporting his immune system.

So here are some things you can do right now that may reduce the risk of your dog getting an autoimmune disease.

• Feed a whole food, raw meat diet with quality proteins and healthy fats. Include fruits and vegetables, organically grown if possible, for antioxidants.
• Add probiotics to balance the beneficial bacteria in your dog’s microbiome and maintain a healthy immune response.
• Include foods that support immunity, like medicinal mushrooms for dogs and omega-3 fatty acids.
• Use inflammation-reducing add-ins like turmeric and ginger.
• Limit your dog’s exposure to chemicals and toxins. Minimize medications, avoid pesticides and chemical products in your home and yard.
• Exercise your dog. Physical activity stimulates healthy blood flow and deep breathing which both support the immune system.
• Manage your dog’s stress level. Give him plenty of outings and opportunities to relax in nature. That’ll be good for your own stress levels too … which can also be a factor in your dog’s mood.

 

DRUGS USED TO CONTROL AUTOIMMUNE SKIN DISEASE 

Glucocorticoids

are the most common group of drugs used to manage autoimmune skin disease. They work by paralyzing receptors (e.g., Fc receptors on macrophages), blocking chemotaxis of inflammatory cells to tissues, and by interfering with production of autoantibodies. The latter probably takes a minimum of 2 to 4 weeks to occur.

Any glucocorticoid can be effective in managing autoimmune disease, although prednisone and prednisolone are considered drugs of choice because they can be administered orally, are relatively inexpensive, have moderate potency, and have a relatively short half-life (to allow sparing the HPA axis with alternate day therapy). The so-called “immunosuppressive” dosage is approximately 2.2 mg/kg daily. Potential side effects are polydipsia, polyuria, polyphagia (and weight gain), and panting; more severe reactions include gastric ulcers, pancreatitis, and secondary infections. The drug is initially given daily for induction, then switched to alternate-day therapy for maintenance, decreasing the total dose by 20% to 25% every 2 to 4 weeks.

Cytotoxic drugs

such as alkylating agents and antimetabolites, are used to decrease antibody production. This therapy probably takes 2 to 4 weeks (minimum) to effectively decrease antibody production. Cyclophosphamide is an alkylating agent commonly used to manage autoimmune diseases, although rarely for skin disease. It has many possible adverse reactions, including: bone marrow suppression, gastroenteritis, transitional cell carcinoma, hemorrhagic cystitis, and alopecia. It is classified by the US Environmental Protection Agency (EPA) as hazardous waste.

Chlorambucil is another alkylating agent that is considered milder than cyclophosphamide. It has fewer side effects, including myelosuppression and anorexia…making it an excellent drug to be used in cats.

Azathioprine

is an anti-metabolite (purine analog) agent. It is given as a dosage of 1 to 2 mg/kg daily for induction, then tapered off during maintenance therapy. Possible adverse effects include gastroenteritis,hepatotoxicosis, pancreatitis, myelosuppression, and neuromuscular blockade (cats). It takes 2 to 3 weeks of therapy to reach the full immunosuppressive effects of this drug. (This means there is a lag period from the time you start therapy, until the time you can expect to see results!) Cats will have more adverse reactions (myelosuppression, neuromuscular blockade) than dogs, and therefore it is not recommended by the author for use in that species.

 

Treatment Options for Autoimmune Skin Diseases

 

Chrysotherapy

is the term for the use of gold salts. Gold is conjugated to other substances, such as sugar [e.g., aurothioglucose (Solganol)] and is available in injectable and oral formulations [auranofin (Ridaura)]. Gold has many mechanisms of action, including inhibition of chemotaxis of inflammatory cells, decreased antibody production (slowly, weeks), inhibition of activation of complement, and decreased phagocytosis. The dosage of the injectable formulation is 1 mg/kg, intramuscularly weekly for induction, then decreased frequency of injections. Possible adverse effects include cutaneous drug reactions (e.g., erythema multiforme), eosinophilia, and thrombocytopenia.

 

Cyclosporine

is a fungal (polypeptide of Tolypocladium inflatum) macrolide that acts as a calcineurin inhibitor. It effectively inhibits interleukin 2 (IL-2) activation, among many other actions. It is metabolized in the liver and excreted in the urine. Because of the mechanisms of action, it provides a very rapid clinical response (hours/days). Induction is usually accomplished with 3 to 5 mg/kg daily. The dose required can be reduced by adding a cytochrome P-450 enzyme inhibitor (e.g., ketoconazole) into the regimen. This is helpful because the drug is quite expensive. It has the potential for many side effects, including gastroenteritis, gingival hyperplasia, papillomatosis, nephrotoxicosis, and secondary infections (all less of a problem when lower doses are used).

 

Leflunomide

is a pyrimidine synthesis inhibitor that has been used primarily in humans as an antirheumatic drug. The drug is converted primarily into teriflunomide, which prohibits expansion of activated lymphocytes by interfering with their cell cycle progression. It has an antiproliferative effect (B and T cells) and an anti-inflammatory effect. Leflunomide has been used in veterinary medicine to manage various autoimmune diseases, and in dermatology, it has been used more often to control pemphigus foliaceus in cases where other therapies have not been successful. It is an expensive drug. Dosages vary in dogs, with most clinicians starting at lower dosages (2–4 mg/kg, PO once daily), then increasing as needed. Possible side effects include vomiting, anorexia, leukopenia, hyper-cholesterolemia, and anemia (at higher dosages)

 

Mycophenalate mofetil

is an immunosuppressive agent that has been used in humans primarily to prevent rejection in organ transplantation. However, it is also used to manage autoimmune diseases, and has been used on dogs to manage autoimmune skin diseases that have responded poorly to other options. Mycophenalate inhibits purine biosynthesis, which results in suppression of T- and B-cell growth. It interferes with DNA replication, thus inhibiting lymphocyte proliferation. Dosages range from 22 to 40 mg/kg, divided 2 to 3 times daily. Potential advantages are rapid onset of action, low toxicity, and availability as a parental preparation. Possible side effects include diarrhea, secondary infections, vomiting, and bone marrow suppression. It is used in veterinary medicine for refractory immune-mediated disease, especially myasthenia gravis.

 

Hydroxychloroquine

is an antimalarial drug that, like many of those agents has effects on the immune system, including decreasing autoantigen presentation to immune cells, the ability to downregulate the expression of cytokines that promote inflammation, and to protect cells from damage from ultraviolet-light. These immunomodulatory effects may be used to manage some autoimmune skin diseases in dogs, such as exfoliative lupus and other forms of lupus erythematosus. The dosage is 5 to 10 mg/kg, PO, once daily. In humans, cardiotoxicity, retinal toxicity, and neuromyotoxicity are potential side effects, although limited reports in dogs have not reported major problems.

 

Doxycycline and niacinamide

is a drug combination used for years in human dermatology. Doxycycline has many immunomodulatory properties. Tetracycline, which may also be used in lieu of doxycycline, suppresses chemotaxis of leukocytes and is synergistic with niacinamide. Niacinamide inhibits IgE-mediated mast cell degranulation and decreases protease release from leukocytes. The advantages of this combination are the safety, which is high (rare to find mild dementia or ataxia with treatment) and low cost. It is not recommended for severe disease; rather is appropriate for mild conditions, such as discoid lupus. The dosages are simple:

• Doxycycline 5–10 mg/kg, q 12 hours OR
• Tetracycline: for dogs <10 kg: 250 mg, every 8 hours; for dogs > 10 kg: 500 mg every 8 hours

PLUS

• Niacinamide: for dogs < 10 kg: 250 mg every 8 hours; for Dogs > 10 kg: 500 mg every 8 hours

The drugs are given at this dose until remission or until maximum benefit is seen (30–60 days), then doses can be decreased (e.g., go to every 12 hours for 30–60 days, etc.) This is an outstanding combination for cutaneous lupus erythematosus (DLE) and other mild autoimmune disorders.

Tacrolimus

is a compound with similar actions as cyclosporine (inhibition of IL-2 through inhibition of calcineurin). It is commercially available as a topical ointment (0.1%). Although expensive, it is used sparingly, so it goes a long way. Tacrolimus is applied twice daily for induction, then in decreasing frequencies for maintenance. Recently, there has been a US Food and Drug Administration (FDA) advisory issued about increased cancer in humans using Protopic over a long-term period of time. It is prudent to advise pet owners to wear gloves when applying this agent.

 

TREATMENT SCHEDULES

Combinations of drugs allow for more rapid response, lower individual drug doses, fewer side effects, and tend to be more successful in controlling autoimmune skin disease. In dogs, azathioprine and prednisone are preferred for induction of MOST autoimmune skin diseases. In cats, chlorambucil and prednisone are preferred for induction. Dosages as previously mentioned are used. We break down therapy into the induction period and maintenance period. Induction is achieved when all old lesions are healed, with the exception of alopecia, and no new lesions are developing. At that time, the doses are slowly reduced during the maintenance period, which is perhaps more appropriately called the tapering-off period.

Patients are monitored during induction with a complete blood count (CBC) and platelet count every 7 to 10 days. In addition, a fecal floatation for endoparasites, also controlled by the immune system, should be done every 2 to 4 weeks. During the maintenance period, a CBC, platelet count, and fecal examination should be performed every 2 to 4 months. It is also wise to monitor the patient with a biochemistry profile and urinalysis every 2 to 4 months.

https://www.pashudhanpraharee.com/common-causes-of-skin-problems-in-dogs/

EDITED & COMPILED BY-DR. AMIT, CANINE SPECIALIST,GOA

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