Autoimmune Disorders in Cats

About

The role of the immune system is to defend the body from pathogens (disease-causing organisms) that can harm the body. Autoimmune disorders refer to a group of diseases in which the cat’s immune system mounts an inappropriate response to the cat’s own cells. Many different cell lines and parts of the body can be the target of an autoimmune disorder, and in some cases, multiple organs are affected.

Antibodies (immunoglobulin G or IgG) are Y shaped proteins produced by specialised white blood cells called B lymphocytes (or B cells) when it encounters a pathogen. Their role is to neutralise invading organisms. There are different antibodies for every pathogen (disease-causing organism) the immune system has encountered. So an antibody to the antigen on the feline herpes virus will not respond to the antigen on the feline calicivirus.

Antibodies tag and bind to antigens (molecules of the pathogen which induce an immune response), which trigger T-cells to engulf the antibody-bound antigen. It takes several days for enough antibodies to be produced to neutralise the pathogen. After this time, antibody numbers decrease; however, memory cells remember the pathogen and if the immune system reencounters it, memory cells spring into action and quickly produce antibodies. This demonstrates why most people only catch diseases such as chickenpox once.

The immune system in cats with autoimmune disorders produces antibodies against the cat’s own tissues (autoantibodies) which leads to their destruction.

Pemphigus

Pemphigus complex is a group of rare bullous autoimmune diseases in cats that results in the formation of superficial vesicles and bullae (a blister that contains serous fluid) which rupture to form crusted erosions on the skin.

Genetic predisposition, exposure to sunlight, certain drugs such as cimetidine and ampicillin, and a history of chronic inflammatory disease are all possible causes.

There are three types of pemphigus in cats:

• Pemphigus foliaceus (PF) – The most common type, affecting the superficial epidermal layers (the top/outermost layer of the skin).
• Pemphigus erythematosus (PE) – The second most common form, affecting the head and feet.
• Pemphigus vulgaris (PV) – A rare form of pemphigus producing blisters in the deep layers of the epidermis. Lesions occur in the mouth and areas of trauma such as claw folds, ears, armpits, and groin. Secondary infections are common and are often fatal.

Symptoms:

• Small red spots and hair loss develop around the eyes and the bridge of the nose, before spreading to the ears, neck, nail beds, on and around the food-pads, nipples, and groin. Small areas of skin discolouration occur before fluid-filled blisters form just beneath the surface of the skin, which rupture and develop into a yellowish crusting erosion.
• As the ears become affected, inflammation (otitis externa) can develop.
• Lameness
• Affected areas are painful and itchy.
• Pemphigus vulgaris affects the mouth, claw folds, ears, armpits (axilla) and groin. Vesicles are easy to rupture, and when they do, deep ulcers form.

Treatment:

Treatment of pemphigus complex can be difficult. It involves immunosuppressive therapy to stop the cat’s own immune system from attacking the tissues.

A large dose is initially administered to induce remission; however, due to the potential side effects of these medications, once remission is achieved, the dose will be tapered to the lowest possible dose to manage the condition.

• Corticosteroid drugs: Prednisolone or methylprednisolone are the first choices of treatment. Small, localised lesions may be responsive to topical therapy, but more widespread cases will require larger immunosuppressive doses to achieve remission.
• Cytotoxic or immunomodulating agents: If remission is not achieved after 7-14 days with the above medications, then other therapies can be added. These include Chlorambucil, a chemotherapy drug, or Azathioprine, a chemotherapy and immunosuppressive drug, Cyclosporine an immunosuppressive drug. Side effects can include vomiting, diarrhea and bone marrow suppression.
• Antibiotics: If a secondary bacterial infection is present.
• Analgesics: Severely affected cats may need painkillers to relieve pain.

Immune-mediated polyarthritis

Immune-mediated polyarthritis is an immune-mediated form of polyarthritis (inflammation of several joints) affecting the movable joints (hips, knees, shoulders). Antibodies bind to the antigen in the joint to form antibody-antigen complexes which are deposited within the synovial membrane; this causes an inappropriate immune response and inflammation within the affected joints.

Immune-mediated polyarthritis falls into two categories, erosive and non-erosive. Erosive polyarthritis destroys the bone cartilage.
Causes include feline leukemia virus, feline immunodeficiency virus, feline syncytium-forming virus and idiopathic (unknown cause). The onset of immune-mediated polyarthritis is between 1-5 years of age.

Symptoms:

• Pain
• Swelling of the affected joint
• Lameness
• Stiffness, especially upon waking
• Holding the affected limb off the ground
• Reluctance to move
• Less active and more cautious (no longer jumping onto/from heights)

Treatment:

• Steroid medications such as prednisolone to treat inflammation, relieve pain and increase mobility.
• Disease-modifying osteoarthritis drugs (DMOAF) are medications that can slow down the progression of the disease. Zydax is an injectable medication that is administered once a week for four weeks.

Home care:

• If your cat is overweight, careful weight loss and increased exercise will be necessary to reduce pressure on the joints.
• Provide warmth to the affected area, which may include the use of a heating pad where your cat sleeps. Keep the bed in a warm and draft-free spot.
• Place litter trays and food bowls in an easily accessible area and if you live in a multi-level house, keep food and water bowls as well as a litter tray on each level.
• Litter trays should have low sides.
• Brush your cat’s coat regularly as grooming is often difficult for a cat with arthritis.
• Trim the claws every six weeks; most veterinary practices will do this for free or at a minimal cost if you can not do this at home.
• Add ramps to high up spots your cat likes to frequent, such as window ledges and cat towers

Systemic lupus erythematosus

First reported in 1971, systemic lupus erythematosus (SLE) is a rare autoimmune disorder that can affect any organ system in the cat. Antibodies are proteins produced by the immune system to counteract and protect the body from antigens such as invading viruses and bacteria. However, sometimes the body produces antibodies against itself (known as auto-antibodies), attacking various systems including the skin, joints, blood vessels, kidneys, heart, and lungs.

The cause of SLE is unknown, although it is thought to be a combination of several factors including genetics, pharmacological agents, environmental, viral infection and exposure to UV light. Siamese, Persians and their related breeds appear to be at greater risk of developing the disease. There is no age or sex predilection in cats.

Symptoms:

Symptoms of SLE depend on the body system affected but can include the following:

Musculoskeletal

• Joint pain and swelling associated with polyarthritis.
• Shifting leg lameness.
• Decreased mobility.
• Muscle weakness.

Renal (glomerulonephritis/kidney disease)

• Enlarged kidneys
• Ascites (fluid in the abdomen)
• Increased thirst
• Increased urination
• Lethargy
• Weight loss
• Vomiting

Dermatologic

• Multifocal alopecia with crusty skin lesions, particularly on the head, face, ears, and rear legs
• Oral ulcers
• Nasal ulcers
• Paronychia (inflammation of the skin around the claws)

Hematologic (hemolytic anemia)

• Depression
• Lethargy
• Pale or yellow mucous membranes
• Anorexia
• Increased heart rate

Hematologic (thrombocytopenia)

• Lethargy
• Blood in urine
• Blood in stool
• Red spots in the eyes and/or gums
• Bruising

Neurological

• Seizures
• Behavioural changes

Other

• Fever with no apparent cause
• Swollen lymph nodes
• Weight changes
• Photosensitivity

Treatment:

There is no cure for SLE and the goal of treatment is to suppress the immune system and improve quality of life.

Medications:

• Nonsteroidal anti-inflammatory drugs (NSAIDs), to reduce inflammation and fever.
• Reduce inflammation with corticosteroids such as prednisone or dexamethasone, tapering the dose once the condition is under control.
• Cyclosporine may be necessary for cats who do not respond to dexamethasone or prednisone.

Note: NSAIDs and corticosteroids should not be given concurrently due to severe side effects, including gastroduodenal ulceration and renal papillary necrosis.

• Limiting exposure to sunlight.
• Splenectomy (removal of the spleen) for severe cases of thrombocytopenia.

Immune-mediated hemolytic anemia

Immune-mediated hemolytic anemia (IMHA), is a disease in which the cat’s own immune system produces antibodies against its own red blood cells. Red blood cells (erythrocytes) supply oxygen to the tissues of the body.

IMHA can be classified as primary or secondary. Primary IMHA is caused by an inappropriate immune response, and no underlying cause can be found. Secondary IMHA is brought about by a drug, toxin (onions, metal objects containing zinc), cancer, parasite or infection which adheres to the red blood cell, altering them to the extent that the cat’s own body no longer recognises them as ‘self’ and initiates a humoral response (antibody production). These antibodies stick to the red blood cells and target them for destruction (hemolysis) by the spleen.

Symptoms:

• Depression
• Lethargy
• Pale or jaundiced (yellow-tinged) mucous membranes
• Weakness
• Loss of interest in food
• Increased heart and respiration rate
• Dark coloured urine
• Uveitis (cloudiness or change in colour to one or both of the eyes)
• Collapse

Treatment:

• Corticosteroids to suppress the immune response.
• Supportive care, such as intravenous fluids where necessary.
• Blood transfusion: If the red blood cells have dropped to critical levels.

Immune-mediated thrombocytopenia

A rare disease in cats, immune-mediated thrombocytopenia occurs when antibodies are formed against a platelet (thrombocyte) antigen. Platelets are made in the bone marrow, their function is to form blood clots. Similar to immune-mediated anemia, there are two types of immune-mediated thrombocytopenia, primary and secondary. It can also run concurrently with immune-mediated anemia or be a part of systemic lupus erythematosus.

The exact cause of primary thrombocytopenia is not known, but it may be due to antigen on thrombocytes closely resembling foreign antigen, hapten formation (haptens are minute molecules that elicit an immune response only when attached to a large carrier such as a protein) and a loss of immune tolerance mechanisms.

Secondary thrombocytopenia can be caused by a viral or bacterial infection, cancer, certain drugs, and tick-borne infections.

Symptoms:

• Lethargy
• Blood in urine
• Blood in the stool
• Red spots in the white of the eyes due to retinal hemorrhage
• Red spots on the gums and skin (petechiae)
• Purple areas on the skin (bruising)

Treatment:

• Mild cases of thrombocytopenia may require no treatment at all.
• Corticosteroids to slow down immune-mediated platelet destruction.
• Transfusion of platelets or whole blood.

Dry eye

Medically known as keratoconjunctivitis sicca (KCS), dry eye syndrome (DES) is a condition characterised by insufficient watery tears reaching the surface of the eye which leads to dryness of the cornea and the conjunctiva. As a result, they become irritated and inflamed due to the lack of lubrication and moisture.

Left untreated corneal ulcers and/or permanent scarring can develop as well as secondary bacterial infection and impaired vision.

There are several causes of dry eye, including immune-mediated inflammation and/or destruction of the tear glands.

Symptoms:

• Excessive blinking
• Thick, stringy mucoid discharge particularly around the rim of the eyes
• Painful red eyes
• Reluctance to open the eyes
• Swollen eyelids
• Dry, dull and opaque appearance to the cornea
• Sensitivity to light (photophobia)

Treatment:

• Cyclosporine is an immune-modulating medication that can suppress immune system inflammation of the tear glands. Administer twice a day. Long-term use is safe, and there are no residual side effects, however, stinging in the eye may occur. It can take several weeks for the effects of cyclosporine to take effect.
• Artificial tears three times a day to keep the eye moist and lubricated. These are the same products people use and are available over the counter from all pharmacies.
• Antibiotics to treat secondary bacterial infections.
• Topical corticosteroids to treat eye inflammation.
• Cats who don’t respond to treatment may require parotid (salivary) duct transposition surgery. This involves moving the parotid duct, which is located in on either side of the cheeks up towards the eyes so they can act as additional tear ducts. Saliva and tears are very similar in composition. While this surgery is usually successful, eye drops may still be required.

Inflammatory bowel disease

Inflammatory bowel disease is a group of disorders caused by the infiltration of inflammatory cells (white blood cells) in the mucosa of the gastrointestinal tract. It can affect both the upper and lower intestinal tract.

• Colitis – Inflammation of the large intestine.
• Enteritis – Inflammation of the small intestine.
• Enterocolitis – Inflammation of the large and small intestine.
• Gastritis – Inflammation of the large and small intestine as well as the stomach.

IBD is the leading cause of chronic vomiting and diarrhea in cats. It can affect cats of any age, although it occurs more often in middle-aged to older cats. Persistent inflammation results in fibrosis (formation of scar-like fibrous tissue), poor digestion and absorption may also result.

The cause of IBD is still unknown although evidence suggests that it could be the result of certain bacteria, dietary allergy or intolerance, genetic influence and parasites causing cats to produce antibodies that attack their own digestive tract.

Increasing attention is being focused on the role of gut microflora (gut microbiome) which are a group of micro-organisms that live in the gut and has many roles such as inhibiting pathogens, metabolic function, assisting the immune system, regulating the production of antibodies.

Symptoms:

Clinical signs vary depending on the region affected.

• Diarrhea (possibly outside the litter tray)
• Lethargy
• Loss of appetite or increase in appetite
• Vomiting
• Weight loss

Treatment:

• Corticosteroids: Prednisone is the drug of choice (as well as dietary therapy) for all types of
  inflammatory bowel disease. These drugs have anti-inflammatory and immunosuppressive properties.
• Antibiotics: Metronidazole is an antibiotic with anti-inflammatory properties and can be used in conjunction with dietary therapy to help manage IBD.
• Other immunosuppressive drugs: Azathioprine (brand name Imuran) is an immunosuppressive drug that can be used in combination with corticosteroids. There can be side effects; it is therefore only used as third-line therapy in refractive (unresponsive to diet and corticosteroids alone) IBD. Cats on this drug should have a CBC every week for the first month and every 2-3 weeks while the cat is on the drug.
• Sulfasalazine: This anti-inflammatory medication is the drug of choice for lymphatic-plasmacytic colitis.
• A highly digestible, low-fat diet containing a novel protein.
• A high fibre diet in cats with colitis
• Fecal transplants are still very new and not readily available yet, but interest in this therapy is growing. It shows great promise for helping cats with digestive issues such as inflammatory bowel disease. A healthy donor with a healthy and diverse microbiome provides a stool sample. This is introduced to the host cat in several ways including colonoscopy, endoscopy, enema or in pill form to restore a diverse microbiome.

Eosinophilic granuloma complex

Eosinophilic granuloma complex (EGC) is a condition characterised by the presence of skin lesions over various parts of your cat’s body.

An eosinophil is a type of white blood cell that participates in allergic reactions and helps to fight certain parasitic infections. A granuloma is an inflammatory lesion that contains granulocytes. These are a type of white blood cell made up of small cytotoxic granules, which are released (degranulation) in response to a microorganism or parasite.

Eosinophil’s job is to attack parasites. Once at the target location, it will release its granules to destroy the parasite. Cats with eosinophilic granuloma complex suffer damage to local tissues due to biochemicals released by eosinophils that are triggered during an allergic response.

Symptoms:

• Indolent ulcer (eosinophilic ulcer or rodent ulcer): This affects cats of all breeds and ages, although it occurs three times as often in females as it is in males. Lesions typically develop on the upper lip, but can also develop on the tongue. They appear as a raised, thickened red/brown ulcer which is well defined and glistening. Generally, while they may look so, they are not painful to the cat.
• Eosinophilic plaque: The lesion can appear on any part of the body, but most often develops on the abdomen or thighs. They appear as red, well-defined, raised, hairless lesions which may be ulcerated.
• Eosinophilic granuloma (linear granuloma or collagenolytic granuloma): This is more common in males than females, and cats under two years old. The back legs are the most common location. Lesions appear as long, straight, thin lines that are raised and inflamed, and pink in colour. Distribution on the face is seen as swellings and nodules on the bottom lip, and the cat has a fat chinned pout. Footpads may also be affected by eosinophilic granuloma.

Treatment:

In addition to addressing the underlying causes outlined above, treatment of the lesions may include:

• Steroids to reduce inflammation.
• Immunosuppressive drugs to suppress the immune system.
• Zyrtec (cetirizine) can help in the treatment of eosinophilic granuloma complex.
• Surgical excision for unresponsive lesions.

Immune-mediated polyneuropathy

This condition affects multiple peripheral nerves (parts of the nervous system outside the brain and spinal cord), which extend to the head, body, and limbs. Sensory (nerves which carry information to the central nervous system), autonomic (nerves which control parts of the body not consciously operated such as heartbeat, digestive system, and pupillary response) and motor (responsible for movement) can be affected resulting in several symptoms depending on the nerves affected.

Symptoms:

Symptoms of immune-mediated polyneuropathy can be acute (sudden onset) or chronic (slow and progressive) and include the following:

• Weakness
• Muscle wasting (atrophy)
• Tremors
• Unsteady gait (ataxia)
• Weakness in the legs
• Paralysis
• Seizures
• Loss of appetite
• Difficulty swallowing
• Regurgitation
• Abnormal neck position

Treatment:

Immunosuppressive drugs such as corticosteroids and azathioprine (Imuran) to suppress the immune system.

Supportive care may include fluid therapy and nutritional support are important for cats who are experiencing difficulty swallowing due to malfunction of the esophagus.

Myasthenia gravis

A congenital or acquired neuromuscular disorder that causes muscle weakness. All muscles are controlled by their own nerve; this nerve doesn’t directly connect to the muscle; there is a small gap between the two which is known as the neuromuscular junction.

For a message to be transmitted from the nerve to the muscle, a chemical messenger called acetylcholine bridges the gap. It travels from the end of the nerve and attaches to the acetylcholine receptor. Cats affected by myasthenia gravis have an abnormal transmission between the two due to antibodies (anti-acetylcholine receptor antibody or AChR antibody) which destroy the acetylcholine receptors, which prevents nerve impulses triggering muscle contraction.

Symptoms:

• Muscle weakness which is worse after periods of activity
• Vocal changes
• Inability to close the eyes fully ( lagophthalmos)
• Gait abnormalities
• Neck ventroflexion
• Regurgitation of food due to megaesophagus (enlargement of the esophagus)
• Drooling

Treatment:

• Immunosuppressive drugs such as cyclosporine or prednisolone to suppress the immune system.
• Feed small, frequent meals, preferably in an upright position for cats with megaesophagus.
• Fluid therapy (subcutaneous or intravenous) to prevent dehydration.
• Antibiotics may be necessary to treat aspiration pneumonia which is common in cats with megaesophagus.