Canine Immune Mediated Diseases short lecture

This presentation discuss about Immune mediated diseases in companion animals

1. Immune Mediated Diseases (Canine & Feline) Abhijith S.P MVSc Scholar Department of Veterinary Medicine Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

2. A strong and healthy immune system is necessary for combating many types of diseases and infections. In healthy dogs and cats, the immune system is tasked with recognizing foreign cells like bacteria or fungi, and then destroying and/or removing them from the body. There are diseases, however, in which the immune system responds inappropriately, and may begin attacking the animal’s own cells. These conditions, as a group, are called immune-mediated disease. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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4. Immune-mediated hemolytic anemia Immune-mediated thrombocytopenia Immune-mediated polyarthritis Myasthenia gravis Immune-mediated skin diseases Keratoconjunctivitis Sicca Glomerulonephritis Immune mediated intestinal disease Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

5. T o reduce and/or eliminate the inappropriate immune response. Mostly, dogs and cats will remain on some kind of immune-suppressive therapy for 4-6 months. Sometimes : therapy continues lifelong. While these immune-suppressive medications are helpful for treating disease, they also pose their own risks . Risk of other infection: HIGH. Basically, immunosuppressants is the basic treatment protocol. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

6. Immune-mediated diseases are not limited to the bloodstream. There are diseases of many body systems that can develop an inappropriate immune response.  For the immune-mediated diseases that attack red blood cells, many dogs and cats will require a blood transfusion to help stabilize them. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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10. S erious and life-threatening condition. Formation of antibody against RBC Surface Antigen/ Direct Macrophage Clearance. With careful treatment, up to 75% of dogs with IMHA can make a full recovery and go on to lead a normal life. M ost common immune-mediated hematologic disorders in dogs and cats In dogs, IMHA is commonly primary or idiopathic in origin, but also occurs secondary to triggers, such as infectious, inflammatory, neoplastic diseases, drugs, vaccines, toxins. In cats, the condition is usually secondary to an underlying cause. New protocols have a much better chance of survival than previously. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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13. PAPERY WHITE ORAL MUCOSAL MEMBRANE Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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19. DIAGNOSIS There is no single test that is definitively diagnostic for IMHA. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

20. “PCV” (Packed Cell Volume) which gives you a quick count red blood cells, reported as a percentage. Normal level of PVC is between 35-55%, with anything less than 35% indicating that your dog is anemic. Total Bilirubin % Reticulocytes / RDW Value Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

21. It is used to determine whether red cell agglutinates are present in a blood sample. When red cell agglutinates are present this indicates that Anaemia is due immune-mediated hemolysis. A blood sample from a dog with IMHA. Note that the blood is "agglutinating” or clumping together – this is a classic sign of IMHA. Note that the plasma (liquid) in the blood is a yellow color, also commonly seen with IMHA. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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23. A positive agglutination test - sample on gross exam (left) and under the microscope (right) Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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27. THERAPEUTIC APPROACH The cornerstone of treatment for IMHA is immunosuppressive therapy . Immunosuppression is usually accomplished with glucocorticoids, with the addition of a second immunosuppressive agent, if needed. Therapy consists of 2 phases: 1. Acute phase, with induction of remission 2. Chronic maintenance phase Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

28. Glucocorticoids have multiple effects on the immune system, but the most important effect for IMHA patients is inhibition of macrophages within the mononuclear phagocytic system. Response to glucocorticoids often takes between 3 and 7 days. Dexamethasone A dosage of 0.3 to 0.5 mg/kg IV Q 24 H is often administered in both cats and dogs. Prednisolone Dogs-1 to 2 mg/kg PO Q 12 H, Cats- 4 mg/kg PO Q 24 H Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

29. Prednisone is a prodrug that is metabolized into prednisolone. When cats receive oral prednisolone, higher plasma concentrations of prednisolone are achieved compared with cats administered oral prednisone; therefore, prednisolone is preferred for use in cats. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

30. Criteria that should prompt consideration of additional immunosuppressive agents include: Severe disease (intravascular hemolysis or transfusion dependency) Marked autoagglutination Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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33. S erious and life-threatening condition. Immune disorder in which the platelet count falls below reference values, as the patient's immune system destroys them. C ommon clinical disorder in which platelets are destroyed by antiplatelet specific antibodies in circulation or at the level of the bone marrow . This can lead to excessive or spontaneous bleeding when platelet counts are less than 30 000 to 50 000/μL. A ntibodies (mainly IgG) bound to the surface of platelets result in their premature destruction by macrophages in the spleen and liver. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

34. Idiopathic IMTP Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

35. Infectious diseases (ehrlichiosis, babesiosis, leishmaniasis, leptospirosis, dirofilariasis, FIV, FIP, and other viral or bacterial infections such as cystitis, prostatitis) Neoplasia ( lymphoma, hemangiosarcoma, mammary tumors) Drugs ( Sulfonamides, vaccines, cephalosporins, phenobarbital) Blood transfusions Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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38. Glucocorticoids have multiple effects on the immune system, but the most important effect for IMHA patients is inhibition of macrophages within the mononuclear phagocytic system. Response to glucocorticoids often takes between 3 and 7 days. Dexamethasone A dosage of 0.3 to 0.5 mg/kg IV Q 24 H is often administered in both cats and dogs. Prednisolone Dogs-1 to 2 mg/kg PO Q 12 H, Cats- 4 mg/kg PO Q 24 H Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

39. Romiplostim is a thrombopoietin receptor agonist that activates intracellular transcriptional pathways via c- Mpl to increase production of platelets. It also works similarly to thrombopoietin (TPO), an endogenous glycoprotein hormone that regulates the production of platelets in the bone marrow. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

40. The extract of papaya leaves has been shown to increase ALOX12 (arachidonate 12-lipoxygenase or platelet type lipoxygenase) by 15 times. This enzyme promotes platelet production via the increased number and differentiation of megakaryocytes. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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42. Immune-mediated polyarthritis (IMPA) is a disease in which the immune system mounts an inflammatory response within the joints causing pain, swelling and difficulty walking. MPA is seen more commonly in dogs than cats, but can occur in both species.  Because the white blood cells are attacking the joints inappropriately, IMPA is referred to as an auto-immune disease. Rheumatoid arthritis is a form of IMPA in people. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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51. GENERAL DIAGNOSTIC ALGORITHM Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

52. PHYSIOTHERAPY Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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55. Myasthenia gravis  is a disease in which there is a malfunction in the transmission of signals between the nerves and muscles. Dogs with myasthenia gravis exhibit extreme weakness and excessive fatigue. Some breeds are predisposed to an inherited/congenital form of this disease, including Jack Russell Terriers, English Springer Spaniels, Smooth Fox Terriers, and Smooth-haired Miniature Dachshunds. "Most cases are acquired, not inherited." Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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66. C lass of medication that inhibits a nervous system enzyme called acetylcholinesterase (Anti-acetylcholinesterase). Because of their compromised ability to swallow, some dogs will actually inhale food, liquid, or vomit, resulting in aspiration pneumonia. Aspiration pneumonia is extremely serious and often requires aggressive intensive care including oxygen therapy, antibiotics, IV fluid therapy, and supportive care. If the dog is unable to eat or drink without regurgitation, a feeding tube may be advised. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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71. 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. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

72. "leaf-like pemphigus" Most common 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. Chow chow , akita, cocker spaniel, Labrador retriever, dachshund, English bulldog, Finnish spitz, and schipperke. Pemphigus foliaceus usually appears suddenly without a recognized cause. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

73. LESION DISTRIBUTION Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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81. 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. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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83. Clinical characteristics of feline pemphigus vulgaris. a - d , f , g : generalized, usually bilaterally symmetrical erosive and ulcerative dermatitis; e : erosive glossitis – a -to- g were taken from the same Siamese cat Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

84. 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. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

85. 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. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

86. The least common (considered extremely rare) most severe type of pemphigus. This condition is associated with the presence of an underlying malignant tumor. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

87. C ommonly 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. B lood 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"). Common in dogs and rare in cats. Nova Scotia duck tolling retriever, Shetland sheepdog, collie, German shepherd dog Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

88. S een in dogs and rarely in cats. C ommon 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. L ess-serious type of systemic lupus erythematosus (SLE). It is considered a relatively benign autoimmune skin disease. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

89. 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. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

90. B M C Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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92. Keratoconjunctivitis sicca (KCS) is a frequent canine ophthalmic disease. D ry eye syndrome, is a chronic ophthalmic disease resulting from deficiency of one or more elements in the precorneal tear film. I nflammatory condition of the ocular surface caused by a pathologic reduction in the aqueous component of the tear film.  Aetiology: congenital, metabolic, infectious, drug induced, neurogenic, radiation, iatrogenic, idiopathic, and immune mediated. Immune mediated: It is a widely primarily accepted cause of KCS. It is generally bilateral Confirmation: Tear Gland Histopathology Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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97. SHIRMER TEAR TEST Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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100. A BETTER RESEARCH TOPIC Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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102. I nflammation of the glomerulus. O ccurs when immune complexes are filtered out of the bloodstream and become trapped within the glomeruli. When these compounds are trapped, the body responds by activating its immune defenses, resulting in further damage to the glomeruli. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

103. TYPE III REACTION IMMUNE COMPLEX MEDIATED Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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105. 1.Treat Underlying Cause 2.Extensive Fluid Therapy (if anuric????) 3.Mild Immunosuppression 4.Repeated Hematology & Serology Estimation. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

106. Leakage of plasma proteins, principally albumin, across the damaged glomerular capillary walls results in persistent proteinuria--the clinicopathological hallmark of glomerulonephritis. Persistent proteinuria is associated with progressive glomerular and tubulointerstitial lesions and loss of additional nephrons In cases of idiopathic glomerulonephritis, angiotensin-converting enzyme inhibitors have been shown to decrease proteinuria and potentially slow disease progression. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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108. Mammalian gastrointestinal tract is colonized by a large number of microorganisms, known as gut microbiota , that play a key role in the physiological and pathological states. In particular, the gastrointestinal tract of dogs and cats harbors a complex and highly biodiverse microbial ecosystem. Due to beneficial effects-GUT MICROBIOTA-”ORGAN”. The immune system produces Ab against the beneficial organism resulting in CHRONIC ENTEROPATHY. Idiopathic Inflammatory Bowel Diseases (IBD). Lymphocytic- plasmacytic enteritis (LPE) is considered to be the most common form of IBD in dogs and, particularly, in cats. Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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110. Digestion Host metabolism Vitamins synthesis (vit. K and complex B) Biotransformation of bile acids Xenobiotics metabolism Correct maturation of gastrointestinal cells Défense against pathogenic bacteria Transformation of primary bile acids Framing of Gut Immune System Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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117. FIGURE 5. Endoscopic images of dogs with IBD consistent with increased small intestinal friability increased small intestinal granularity intestinal mucosal erosions (D) Endoscopic image showing the advancement of biopsy forceps to obtain partial-thickness biopsy samples in a dog with inflamed GI mucosa and IBD.  Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

118. TREATMENT MANAGEMENT Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)

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123. THANK YOU Dr Abhijith S.P. (M.V.Sc Veterinary Medicine)