Immunology AI Flashcards
What are the expected events after injection of a vaccine in a healthy animal?
- Virus infects host cells, causing lysis of some cells
- Viral proteins are taken up by resident dendritic cells and processed for presentation on MHC molecules
- Dendritic cells are activated when their PRRs recognise typical viral structures or DAMPs released from dying cells
- Dendritic cells carrying viral antigens migrate to local lymph nodes
- Dendritic cells interact with naïve T cells in the lymph node, activating any T cells that recognise the viral antigens on their MHC molecules
- Activated T cells provide help to B cells in the lymph node that also recognise viral antigens
- Activated B cells differentiate into plasma cells and produce antibodies specific for the virus
- Antibodies and activated T cells clear the virus from infected tissues.
Why is vaccination able to make use of the memory response of the immune system?
Immune responses develop more quickly and effectively after repeated exposure to the same antigens.
What are memory T and B cells?
They are long-lived cells produced during immune responses that are able to respond directly to their antigen, permitting more rapid production of antibodies by B cells, production of cytokines by CD4+ T cells, or generation of activated cytotoxic (CD8+) T cells.
What route of vaccination is commonly used in veterinary practice?
Most vaccines used in veterinary practice are administered by subcutaneous injection, where they will be absorbed systemically to generate an immune response in the lymph nodes and spleen.
Why is stimulation of local, mucosal immunity important for pathogens that normally infect mucosal surfaces?
Protective immunity depends on stimulation of local, mucosal immunity. Immune responses can be generated in mucosa-associated lymphoid tissue (MALT), rather than in the lymph nodes or spleen.
Where are mucosa-associated lymphoid tissues typically found in the body?
Mucosal tissues of the respiratory, gastrointestinal, and urogenital tracts.
What are autoinflammatory diseases and how are they different from autoimmune diseases?
Autoinflammatory diseases are caused by inappropriate activity of the innate immune system without activation of T cells or other components of the adaptive immune system. Autoimmune diseases, on the other hand, involve the immune system attacking normal cells and tissues.
Why are some diseases in veterinary medicine described as ‘immune-mediated’?
Some diseases in veterinary medicine are described as ‘immune-mediated’ because it isn’t clear whether they are autoimmune or autoinflammatory. Detailed research studies are often lacking to establish the exact cause of these diseases.
What is the association between autoimmune haemolytic anaemia and chronic lymphocytic leukaemia?
There is a strong association between the development of autoimmune haemolytic anaemia and underlying chronic lymphocytic leukaemia, where the malignant B cells produce autoantibodies causing red blood cell destruction.
Why do thymomas frequently develop myasthenia gravis?
Thymomas frequently develop myasthenia gravis due to the inappropriate production of antibodies against the acetylcholine-gated ion channels in the neuromuscular junction.
How do some drugs increase the risk of autoimmune reactions?
Some drugs increase the risk of autoimmune reactions by possibly changing the expression of genes that regulate the immune system or altering the structure of normal proteins in the body, causing the immune system to identify them as foreign.
Do vaccinations have a proven association with autoimmune disease in dogs and cats?
No, there is no proven association between vaccination and autoimmune disease in dogs and cats, although it is frequently reported anecdotally and included as a warning in the datasheet of some vaccine products.
What is molecular mimicry and how does it relate to autoimmune diseases?
Molecular mimicry is when bacteria or pathogens have molecular structures that are similar to normal host molecules. In some cases, the immune response against the pathogen may ‘cross-react’ with host tissues, leading to immune-mediated damage.
What role does the microbiome play in shaping the immune system?
The microbiome, consisting of bacteria, viruses, and fungi in the gut, upper respiratory tract, and on the skin, interacts with the immune system to shape its development and immune responses. Mice raised in sterile conditions, without a microbial community, have a decreased risk of many autoimmune diseases.
Are there any recommended interventions targeted at the microbiome for dogs and cats with immune-mediated diseases?
Currently, there is insufficient evidence to recommend probiotics, antibiotics, or any other intervention targeted at the microbiome in dogs and cats diagnosed with an immune-mediated disease.
What diagnostic tests may be considered when presented with a dog or cat showing signs of an autoimmune disease?
When presented with a dog or cat showing signs of an autoimmune disease, clinicians may consider performing a thorough history, including exposure to drugs and toxins, physical examination, and checking all peripheral lymph nodes.
What is the difference between immune-mediated (IMHA) and autoimmune (AIHA) diseases in dogs and cats?
In dogs and cats, diseases such as haemolytic anaemia are described as immune-mediated (IMHA) if they are specific for a normal self-antigen, while they are described as autoimmune (AIHA) if they are caused by an autoimmune response.
What are the general clinical features of autoimmune and autoinflammatory diseases?
The general clinical features of autoimmune and autoinflammatory diseases may differ depending on their causes. Autoimmune diseases depend on the location of the targeted self-antigen, while autoinflammatory diseases exhibit features similar to an acute phase response.
Give an example of an autoimmune disease where the antigen is expressed in a single location.
Autoimmune (lymphocytic) thyroiditis is an example of an autoimmune disease where the antigen is expressed in a single location, specifically the thyroid gland.
What autoimmune disease in dogs exhibits immune responses against nuclear proteins produced throughout the body?
Systemic lupus erythematosus, a rare autoimmune disease in dogs, exhibits immune responses specific for nuclear proteins produced in practically every cell in the body.
What are the clinical signs of autoinflammatory diseases?
Autoinflammatory diseases typically display features of an acute phase response, including intermittent fever, lethargy, malaise, generalized lymph node enlargement, and occasionally joint pain and arthritis.
What combination of mechanisms can some diseases involve?
Some diseases can involve a combination of autoinflammatory and autoimmune mechanisms, where they may begin as an autoinflammatory disease and progress to an autoimmune response if T cells become activated.
Which disease causes pyrexia, joint pain, swelling, inflammation, and deposition of amyloid proteins in multiple tissues?
Shar Pei fever, also known as Shar Pei Autoinflammatory Disease (SPAID), causes pyrexia, joint pain, swelling, inflammation, and deposition of amyloid proteins in multiple tissues.
What is the cause of primary hypoadrenocorticism in most cases?
In most cases of primary hypoadrenocorticism, the cause is an autoimmune response directed against antigens found only in the adrenal glands.
What are the learning objectives of this module?
The learning objectives are to distinguish between the innate and adaptive responses, describe the major cell types associated with innate and adaptive immune responses, interpret the major components of adaptive immune response, describe the types of functions of antibodies, explain what immunity neonatal animals possess due to transplacental and transmammary transfer, describe the major changes that occur in the immune system with a vaccine, describe the different types of vaccine available, with reference to those clinically available, and distinguish between autoimmune and autoinflammatory diseases.
What does the immune system protect against?
The immune system provides protection against infectious pathogens, some cancers, and is responsible for removing senescent cells and debris in the blood and central nervous system.
How can the immune system be defined?
The immune system can be defined by its structural components, meaning the cells and tissues that contribute to the immune system, or by its functional elements and actions, regardless of which cells and tissues are actually performing these actions.
What are the barriers to infection in the normal mammalian body?
The normal mammalian body provides several barriers to infection at the skin and internal mucous membranes. These include physical separation of exogenous organisms from critical internal organs, as well as physical and chemical properties of these surfaces that prevent colonization of bacteria and other pathogens.
What are innate immune responses?
Innate immune responses are not specific to a single antigen but are activated by molecular signatures shared by many different pathogens. They occur rapidly and consistently because they are initiated by cells that are already resident in the tissue.
What are the clinical features of inflammation?
The typical clinical features of inflammation are described using a set of Latin terms. One of these features is dolor, which refers to the pain caused when inflammatory mediators activate receptors on neurons.
What are some cytokines that may be released into the blood in large quantities?
Interleukin-1β (IL-1β), TNFɑ, and interleukin-6 (IL-6).
What is the purpose of the acute phase response?
To direct the body’s resources towards fighting infection and create an environment that is not conducive to pathogen replication.
What are the typical features of the acute phase response?
Pyrexia, increased serum c-reactive protein (CRP), mild non-regenerative anemia, and inflammatory leukograms consisting of neutrophilia with monocytosis.
What causes the increase in neutrophils and monocytes in dogs with tissue inflammation?
The effect of inflammatory cytokines on myeloid progenitors in the bone marrow, increasing the production of mature myeloid cells.
What is the difference between innate immune responses and adaptive immune responses?
Innate immune responses occur quickly and reliably in any damaged or infected tissue, while adaptive immune responses mount powerful responses against specific antigens and develop immunological memory.
Where do T cells undergo rounds of selection?
In the thymus.
Where do B cells undergo selection?
In the bone marrow.
What is fixed before birth and does not change during life?
The range of pathogens that can be recognized by innate immune cells due to the inheritance of genes encoding PRRs (Pattern Recognition Receptors) from parents.
What are the two types of antibodies produced by B cells?
The two types of antibodies produced by B cells are IgM and IgE.
What is the major function of IgE antibodies?
The major function of IgE antibodies is to cause degranulation of mast cells, leading to localized or systemic inflammatory responses.
What is opsonization?
Opsonization is the process of marking bacteria for phagocytosis by neutrophils.
What is antibody-dependent cell cytotoxicity (ADCC)?
Antibody-dependent cell cytotoxicity (ADCC) is the process of marking infected cells for destruction by cytotoxic (CD8+) T cells.
Which type of antibodies are particularly effective in activating the complement cascade?
IgM antibodies are particularly effective in activating the complement cascade.
How do neonatal dogs and cats obtain maternal antibodies?
Neonatal dogs and cats obtain maternal antibodies through the placenta (5-10%) and absorption across the gastrointestinal tract after ingestion of colostrum (90-95%).
What is immunosenescence?
Immunosenescence is the general trend for animals to mount less effective immune responses with increasing age, making them more susceptible to infectious diseases.
What type of cells does the thymus produce more of in neonatal dogs and cats?
The thymus produces more CD4+ T cells than CD8+ T cells in neonatal dogs and cats.
What is the process of shuffling gene segments called?
The process of shuffling gene segments is called gene rearrangement.
What is the main difference between adaptive and innate immune responses in terms of specificity?
Adaptive immune responses are much more specific to the inciting cause than innate responses.
Where does the initiation of adaptive immune responses usually take place?
The initiation of adaptive immune responses is usually confined to specialised lymphoid organs.
What do resident dendritic cells (DCs) collect in inflamed or damaged tissues?
Resident dendritic cells (DCs) collect proteins in inflamed or damaged tissues.
With what molecules do dendritic cells display digested fragments of collected proteins?
Dendritic cells display digested fragments of collected proteins in conjunction with molecules called major histocompatibility complexes (MHC, class II).
What happens when a helper T cell recognizes an antigen displayed by a dendritic cell?
When a helper T cell recognizes an antigen displayed by a dendritic cell, a strong interaction is formed between the two and the dendritic cell stimulates the T cell to proliferate and differentiate.
What are the two types of cells that B cells can differentiate into when stimulated by activated helper T cells?
When stimulated by activated helper T cells, B cells can differentiate into plasma cells or memory B cells.
Which type of antibody in mammals is the most common isotype in the serum?
The most common isotype of antibody in the serum of mammals is IgG.
What are immune complexes?
Immune complexes are large, complex aggregates composed of antibodies and antigens.
Where are immune complexes preferentially deposited?
Immune complexes are preferentially deposited in the glomerular capillaries and synovial membranes.
What can cause glomerulonephritis?
Local activation of the complement cascade and infiltration of immune cells caused by deposition of immune complexes can cause glomerulonephritis.
What can cause immune-mediated polyarthritis?
Local activation of the complement cascade and infiltration of immune cells caused by deposition of immune complexes can cause immune-mediated polyarthritis.
What cells are activated in some autoimmune diseases?
CD8+ (cytotoxic) T cells can be activated in some autoimmune diseases.
What do the activated CD8+ T cells do in autoimmune response?
Activated CD8+ T cells destroy cells bearing the antigen that stimulated the autoimmune response.
What breeds are autoimmune diseases classically seen with increased frequency in?
Autoimmune diseases are classically seen with increased frequency in the Cocker spaniel.
What environmental factors can contribute to the development of autoimmune diseases?
Environmental factors such as gender and neutering status, infections, ingestion of some drugs, and exposure to ultra-violet light can contribute to the development of autoimmune diseases.
What are the observed changes in B and T cells?
There is a general reduction in the numbers of B and T cells.
What is the immune system difference between German shepherd dogs and other breeds?
German shepherd dogs have a selective deficiency in the production of IgA antibodies.
Where are IgA antibodies made?
IgA antibodies are made at mucosal surfaces.
What is the concentration of IgA in German shepherd dogs compared to other breeds?
The concentration of IgA is lower in German shepherd dogs in blood and bile than in other breeds.
What has been suggested about the deficiency in IgA in German shepherd dogs?
This deficiency in IgA may increase the risk of inflammatory bowel disease in German shepherd dogs.
What does vaccination involve?
Vaccination involves administration of an attenuated version or part of a pathogen to stimulate an immune response.
What do most vaccines aim to do?
Most vaccines aim to limit the extent of disease or clear the pathogen more quickly.
What is the purpose of adjuvants in vaccines?
Adjuvants stimulate the innate immune system to ensure an immune response develops.
What could be a sign of lymphoproliferative disease?
Gross enlargement of lymph nodes.
What imaging techniques can be used to check for masses or internal lymph node enlargement in the thorax and abdomen?
Thoracic radiographs and abdominal ultrasonography.
What should be considered when there is a travel history?
Testing for infectious agents, particularly Babesia canis and Ehrlichia canis in dogs that have not traveled abroad.
In what cases should tests for infectious agents be considered even in dogs that have always been in the UK?
If there have been reports of Babesia canis and Ehrlichia canis in dogs in the UK that have not traveled abroad.
What is often requested to check for urinary tract infection?
Urinalysis with culture.
What is difficult to establish when urinary tract infections are found?
Whether UTIs are the cause for autoimmune diseases or if they are simply concurrent.
What is the term for the feeling of heat caused by increased blood flow to the tissue?
Calor
What is the term for the redness of the tissue that occurs when inflammatory mediators cause vasodilation?
Rubor
What is the term for the swelling of the tissue caused by leakage of fluid and protein across blood vessel walls?
Tumor
What is the term for the loss of normal function caused by altered blood flow or infiltration of inflammatory cells?
Functio laeso
Which cells in the tissue initiate inflammatory responses?
Tissue macrophages, mast cells, and endothelial cells
What are the molecular patterns shared by infectious agents or molecules released when tissues are damaged?
Pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs)
What are the inflammatory mediators produced by activated resident cells?
Histamine, prostaglandins, and cytokine tumor necrosis factor alpha (TNFɑ)
What are the principal myeloid cells recruited to the site of inflammation?
Neutrophils, monocytes, and eosinophils
What is Feline Immunodeficiency Virus (FIV) commonly associated with in cats?
FIV is commonly associated with immunological complications and chronic, non-regenerative anemia due to bone marrow dysfunction.
How is immune-mediated hemolytic anemia (IMHA) diagnosed in cats?
IMHA in cats is diagnosed based on a positive direct antiglobulin test (DAT) and/or in-saline agglutination since spherocytes cannot be reliably detected.
What is the significance of ‘ghost cells’ in cats with IMHA?
‘Ghost cells’ are red blood cell remnants that persist after hemolysis. While they may be associated with IMHA in cats, they are not specific to immune-mediated disease and can also be observed with oxidizing toxins like paracetamol.
Was it previously believed that IMHA in cats was more likely to be associated with an underlying disease compared to dogs?
Yes, it was traditionally suggested that IMHA in cats was more likely to have an underlying disease, but larger studies have shown that approximately 60-75% of cats with IMHA have no detectable underlying cause.
What are the possible patterns observed in bone marrow samples of dogs and cats with non-regenerative IMHA?
Bone marrow samples may reveal strongly regenerative response (erythroid hyperplasia) in the bone marrow with peripheral non-regenerative anemia, lack of a regenerative response (erythroid hypoplasia) in the bone marrow with peripheral non-regenerative anemia, or complete absence of erythroid stem cells (pure red cell aplasia) in the bone marrow.
What immediate care measures can be taken for dogs and cats with IMHA?
In cases of acute anaemia causing cardiovascular compromise, blood transfusion is indicated in dogs with signs of compromise. Packed red blood cells are preferable to fresh whole blood in dogs with IMHA.
Is there a standard trigger for blood transfusion in dogs with IMHA?
No, there is no standard trigger for transfusion as it depends on factors like the speed of onset of anaemia, the severity of the anaemia, and the severity of clinical signs.
How can Babesia canis be detected in red blood cells?
Babesia canis can be detected in red blood cells in fresh blood smears by a trained pathologist.
What is the recommended action if a dog has a travel history to (Southern) Europe or an area with reported cases of B. canis?
It is recommended to have a blood sample examined at an external laboratory and request polymerase chain reaction (PCR) for B. canis.
Which breed of dogs are born with defects in enzymes required for normal metabolism inside red blood cells?
Dogs of some breeds, such as English Springer spaniels, are born with defects in enzymes required for normal metabolism inside red blood cells.
What is the most common disease causing severe haemolysis in dogs after exercise or excitement?
The most common disease causing severe haemolysis in dogs after exercise or excitement is phosphofructokinase (PFK) deficiency.
Which breed has been diagnosed occasionally with phosphofructokinase (PFK) deficiency?
English Springer spaniels have been diagnosed occasionally with phosphofructokinase (PFK) deficiency.
What is the other reported disease that can cause mild, chronic haemolytic anaemia in dogs?
The other reported disease that can cause mild, chronic haemolytic anaemia in dogs is pyruvate kinase (PK) deficiency.
Which breed is known to have a reported association with pyruvate kinase (PK) deficiency in the UK?
West Highland white terriers are known to have a reported association with pyruvate kinase (PK) deficiency in the UK.
What are some causes of haemolysis other than phosphofructokinase (PFK) deficiency or pyruvate kinase (PK) deficiency?
Some other causes of haemolysis include severe acute leptospirosis, oxidising toxins like zinc, onions, and paracetamol in cats, and Mycoplasma haemocanis transmitted by tick bites.
What is ITP?
ITP stands for immune-mediated thrombocytopenia, a condition characterized by a low platelet count due to immune destruction of platelets.
What are some variants of ITP?
Some variants of ITP include Angiostrongylus vasorum, which is associated with lungworm infestation, and a ‘non-regenerative’ form in dogs where megakaryocytes in the bone marrow are targeted.
How can lungworm infestation be detected in dogs suspected of having IMTP?
Lungworm infestation can be detected using either a SNAP test on blood or Baermann flotation of a fecal sample in dogs suspected of having immune-mediated thrombocytopenia (IMTP).
In the study mentioned, what was the difference between dogs with regenerative and non-regenerative forms of IMTP?
Dogs with non-regenerative forms of IMTP had a poorer prognosis, were more likely to require blood transfusion, and were more likely to be anemic at the time of presentation compared to dogs with normal numbers of megakaryocytes in the bone marrow.
Is primary IMTP common in cats?
Primary immune-mediated thrombocytopenia (IMTP) is rarely reported in cats and seems to be much less common than in dogs.
What are some other underlying causes of thrombocytopenia in cats?
Other underlying causes of thrombocytopenia in cats include feline leukemia virus and feline immunodeficiency virus infections.
What immediate treatment is advised for dogs with confirmed thrombocytopenia?
Dogs with confirmed thrombocytopenia should be handled carefully, and jugular venepuncture should be avoided. It is also advisable to administer a gastric acid suppressant, such as omeprazole, and dogs with IMTP and anemia may require blood transfusion.
Are platelet transfusions a viable treatment option for thrombocytopenic dogs?
Platelet transfusions are not a viable treatment option for thrombocytopenic dogs due to the short half-life of platelets and their susceptibility to damage or activation during transfusion.
What are the two possible causes of neutropenia?
Neutropenia may be caused by decreased production of neutrophils in the bone marrow or by increased consumption or destruction of neutrophils in the periphery.
What is the typical appearance of a ‘left shift’ in neutropenia?
The bone marrow responds to peripheral destruction of neutrophils by increasing production and releasing immature (band) neutrophils into the circulation, producing a ‘left shift’.
What is one common cause of neutropenia?
Severe bacterial infections and sepsis are often a common cause of neutropenia.
Why is it important to collect diagnostic samples prior to starting antimicrobials?
Collecting diagnostic samples prior to starting antimicrobials helps establish whether an infection is the cause or result of the neutropenia.
What investigations are commonly performed to exclude sepsis or a septic focus in a dog with neutropenia?
Imaging of the thorax and abdomen, collection of sterile urine sample for culture, collection of sterile samples from abnormal sites, echocardiography, and collection of blood samples for blood culture.
What is the pathogenesis of Immune-Mediated Neutropenia (IMNP)?
The pathogenesis of IMNP involves an autoimmune response against normal antigens on the surface of neutrophils, resulting in production of antibodies that facilitate their phagocytosis and removal by phagocytes in the spleen.
What is one recommended test for detection of anti-neutrophil antibodies in suspected IMNP?
Flow cytometry test for detection of anti-neutrophil antibodies is recommended in suspected IMNP cases.
What other tests are recommended to rule out other causes of neutropenia in IMNP cases?
Testing for vector-borne pathogens, sampling the bone marrow to exclude pathology or neoplasia, and investigations to exclude underlying causes for immune-mediated neutropenia.
What is immune-mediated polyarthritis?
Immune-mediated polyarthritis is a condition that may occur in cats, but is less common than in dogs. It is characterized by inflammation in multiple joints.
Which clinical syndrome is commonly reported in young adult male neutered cats with polyarthritis?
A particular clinical syndrome called periosteal proliferative polyarthritis (PPP) is commonly reported in young adult male neutered cats with polyarthritis.
What causes erosive lesions in cats with polyarthritis?
Polyarthritis in cats can cause erosive lesions, particularly affecting the distal joints (carpi and tarsi).
What percentage of dogs with steroid-responsive meningitis arteritis (SRMA) may experience inflammation of the peripheral joints?
As many as 30% of dogs with SRMA may experience inflammation of the peripheral joints.
What is the immediate treatment approach for dogs and cats with suspected immune-mediated polyarthritis (IMPA)?
Before receiving diagnostic results, dogs and cats with suspected IMPA can be administered analgesic and antipyretic medication like paracetamol to improve their quality of life.
What type of medication can be concurrently used with steroids for analgesia in dogs with IMPA?
Paracetamol can be used concurrently with steroids for analgesia in dogs with IMPA, unlike conventional NSAIDs.
What is the safe and suitable dose of dexamethasone for anti-inflammatory treatment in dogs with strong suspicion of IMPA?
A safe and suitable dose of 0.1 mg/kg dexamethasone IV once daily can be administered for anti-inflammatory treatment in dogs with strong suspicion of IMPA.
What are multi-systemic immune-mediated diseases?
Multi-systemic immune-mediated diseases are immune-mediated diseases that appear to affect multiple different tissues due to autoimmune responses directed against several different antigens.
What are the major clinical and clinicopathological features of immune-mediated haemolytic anaemia in dogs and cats?
The major clinical and clinicopathological features of immune-mediated haemolytic anaemia in dogs and cats need to be described.
What clinical tests can be used to make a definitive diagnosis of IMHA in dogs?
The clinical tests that may be used to make a definitive diagnosis of IMHA in dogs should be described.
What are the other possible causes of haemolysis in dogs?
The other possible causes of haemolysis in dogs and how they may be excluded with appropriate tests need to be discussed.
What are the major clinical and clinicopathological features of immune-mediated thrombocytopenia and neutropenia in dogs and cats?
The major clinical and clinicopathological features of immune-mediated thrombocytopenia and neutropenia in dogs and cats should be described.
How can a definitive diagnosis of IMTP and IMNP in dogs be made?
The clinical tests that may be used to make a definitive diagnosis of IMTP and IMNP in dogs should be discussed.
What are the other possible causes of thrombocytopenia and neutropenia in dogs?
The other possible causes of thrombocytopenia and neutropenia in dogs and how they may be excluded with appropriate tests need to be discussed.
What are the major clinical and clinicopathological features of immune-mediated polyarthritis and multi-systemic diseases in dogs and cats?
The major clinical and clinicopathological features of immune-mediated polyarthritis and multi-systemic diseases in dogs and cats should be described.
How can a definitive diagnosis of IMPA, erosive polyarthritis, and SLE in dogs be made?
The clinical tests that may be used to make a definitive diagnosis of IMPA, erosive polyarthritis, and SLE in dogs should be discussed.
What are the other possible causes of joint effusion in dogs?
The other possible causes of joint effusion in dogs and how they may be excluded with appropriate tests need to be discussed.
Why should blood be cooled or refrigerated?
Blood should be cooled or refrigerated because this may cause non-pathological agglutination in some dogs.
What can cause false positive results in agglutination tests?
Agglutination tests may produce false positive results because it may occur in dogs with other diseases.
What is the significance of macroscopic agglutination in the diagnosis of IMHA?
Macroscopic agglutination can be observed in dogs with IMHA and it needs to be subjectively interpreted.
What are spherocytes and how are they related to the diagnosis of IMHA?
Spherocytes are small red blood cells that lack normal central pallor and are observed in dogs with IMHA. They are thought to develop when a macrophage in the spleen partially phagocytoses the cell, causing changes in its structure.
Can spherocytes be reliably detected in cats? Why or why not?
Spherocytes cannot be reliably detected in cats because their red blood cells are smaller and often lack central pallor when observed microscopically.
Why is it recommended to perform additional tests after establishing a diagnosis of IMHA?
Additional tests are recommended to determine if there is an underlying cause of IMHA, as it is present in approximately 20-25% of cases.
What is the most common underlying cause of IMHA?
Cancer, particularly lymphoma or other forms of lymphoproliferative disease, is the most common underlying cause of IMHA.
Which drugs have been associated with IMHA?
Antimicrobials of the beta lactam and sulphonamide classes have been associated with IMHA in dogs.
What is the defining feature of IMHA?
The defining feature of IMHA is the presence of antibodies directed against red blood cells.
What test is used to detect antibodies bound to red blood cells?
The direct antiglobulin test (DAT, Coombs’ test) is used to detect antibodies bound to red blood cells.
How is the result of the direct antiglobulin test (DAT) expressed?
The result of the DAT is expressed as a titre, indicating the lowest concentration of Coombs’ reagent needed to cause agglutination.
What is considered a ‘high’ titre result in the direct antiglobulin test (DAT)?
A ‘high’ titre in the DAT (e.g., 1/256) indicates that only a small amount of the antiserum is needed to cause agglutination.
What is the sensitivity of the direct antiglobulin test (DAT) for IMHA?
The DAT has a sensitivity of approximately 66%, meaning that 66% of tested dogs with IMHA will have a positive result.
What is the specificity of the direct antiglobulin test (DAT) for IMHA?
The DAT has a specificity of approximately 90%, meaning that 10% of tested dogs that do NOT have IMHA will have a positive result.
Why was the direct antiglobulin test (DAT) previously out of favour?
The DAT used to take several days to come back from diagnostic laboratories, which could delay treatment. However, there are now ‘point of care’ DATs that provide results in minutes.
How can agglutination of blood be appreciated in dogs with IMHA?
Agglutination of blood can be appreciated by diluting a drop of blood in saline or by mixing one drop of fresh blood with one drop of saline on a slide, then examining for evidence of agglutination.
What is a major cause of thrombocytopenia in dogs?
Destruction of platelets caused by an autoimmune response directed against normal antigens on their surfaces.
What can cause increased consumption of platelets?
Thromboembolic diseases, disseminated intravascular coagulation (DIC), and some infectious agents.
What infectious agents are associated with mild thrombocytopenia in animals?
Leptospirosis, Angiostrongylus vasorum, Ehrlichia canis, Anaplasma phagocytophilum, and Babesia canis.
What does reduced production of platelets imply?
A problem with the bone marrow where platelets are released as fragments from megakaryocytes.
What can cause platelets to become sequestered inside blood-filled spaces?
Splenic enlargement or splenic tumors.
How can one establish if a dog or cat has immune-mediated thrombocytopenia (IMTP)?
Performing tests that detect antibodies bound to the surface of platelets, though these tests require validation.
What is a helpful feature observed in dogs with immune-mediated thrombocytopenia (IMTP)?
The platelet count is normally extremely low (<20x109/l) and may be associated with microplatelets.
What are some common underlying causes for IMTP in dogs?
Cancer (lymphoma), infectious diseases (Anaplasma phagocytophilum, Ehrlichia canis, Babesia canis), and exposure to drugs and toxins.
What are some endocrine diseases that can occur in dogs?
Some endocrine diseases that can occur in dogs include hypothyroidism, hypoadrenocorticism, hypoparathyroidism, and diabetes mellitus.
What is autoimmune polyglandular syndrome?
Autoimmune polyglandular syndrome is when combinations of endocrine diseases occur in the same individual, often accompanied by an immune response.
What are the clinical syndromes associated with type 1 autoimmune polyglandular syndrome in people?
The clinical syndromes associated with type 1 autoimmune polyglandular syndrome in people are concurrent adrenal insufficiency, hypoparathyroidism, and decreased gonadal function.
What is systemic lupus erythematosus (SLE)?
Systemic lupus erythematosus is a complex autoimmune disease that can affect multiple tissues within the body and is associated with an immune response against nuclear antigens.
What are the major immunological effector mechanisms implicated in causing tissue damage in SLE?
The major immunological effector mechanisms implicated in causing tissue damage in SLE include production of antibodies against cellular components, formation of immune complexes, and T cell reactions to normal antigens.
What are some common clinical features of SLE in people?
Some common clinical features of SLE in people include fever, generalised lymph node enlargement, haemolytic anaemia and/or thrombocytopenia, polyarthritis, glomerulonephritis, and ulcerative skin lesions or ulcers within the mouth.
What should be suspected in a dog presented with polyarthritis and concurrent skin lesions?
SLE should be suspected in a dog presented with polyarthritis and concurrent skin lesions.
What may produce a ‘haemic’ cardiac murmur in dogs with IMHA?
The increased likelihood of turbulent flow due to reduced haemoglobin concentration in the blood.
How can pallor be caused in dogs with IMHA?
The reduced haemoglobin concentration in the blood.
How can pre-hepatic icterus be caused in dogs with IMHA?
Severe haemolysis may cause pre-hepatic icterus.
How can haemoglobinuria be observed in dogs with IMHA?
Excess quantities of free haemoglobin released from lysed red blood cells are excreted in urine.
What are the most frequent signs observed in dogs with IMHA according to the course notes?
Non-specific and progressive lethargy, and reduced exercise tolerance.
What are common episodes seen in dogs with IMHA?
Episodes of syncope, particularly when dogs try to run or become excited.
What are some possible reasons for dogs with IMHA having a history of vomiting?
Possibly related to hypoxia of the gastrointestinal tract or the effect of excess bilirubin, which causes a feeling of nausea in people.
What is the pathogenesis of immune-mediated haemolytic anaemia (IMHA)?
IMHA is an autoimmune disease where the immune system mounts an adaptive immune response against glycophorin molecules on the surface of red blood cells.
What is the purpose of using anti-inflammatory drugs in controlling pyrexia?
The purpose of using anti-inflammatory drugs is to control pyrexia.
What drug has been suggested for slowing down the development of fibrosis?
Colchicine has been suggested for slowing down the development of fibrosis.
Is there any evidence to support the claim that colchicine slows the development of amyloidosis?
There is currently no evidence to suggest that colchicine slows the development of amyloidosis.
What should be done if proteinuria is detected in affected dogs?
If proteinuria is detected in affected dogs, appropriate therapies should be introduced, including ACE inhibitors or angiotensin receptor antagonists, moderately protein-restricted diet, and control of hypertension if this develops concurrently.
What should be monitored closely in affected dogs?
Affected dogs should be monitored closely for the development of proteinuria.
What is discussed further in the renal module relating to the management of proteinuria?
The management of proteinuria is discussed further in the renal module.
What is the most useful test for investigation of joint effusions?
Sampling the synovial fluid.
How many different joints should be sampled in dogs suspected of having Immune-Mediated Polyarthritis (IMPA)?
At least 3 different joints.
What is the recommended sampling procedure for synovial fluid in dogs suspected of having IMPA?
Sampling both carpi and both tarsi, even though the stifles are easier to sample.
What are the characteristics of normal synovial fluid?
It should be colorless or a light straw color, viscous, and yield a very small amount of fluid.
What should be done if there is only a small amount of synovial fluid available for analysis?
Small drops should be put on several slides and smeared to allow drying.
What tests should be conducted if septic arthritis is considered possible?
Bacterial culture can be done using a charcoal swab or by injecting some fluid into a blood culture bottle.
What major parameters are measured in synovial fluid analysis?
Color, viscosity, volume, nucleated cell count, protein concentration, and cytology.
What are the types of Immune-Mediated Polyarthritis (IMPA)?
Erosive and non-erosive types.
Why is there little benefit to providing supplemental oxygen to dogs with IMHA?
Because the amount of oxygen dissolved in blood is a tiny fraction of the amount carried on haemoglobin molecules.
What is the priority in treating dogs with IMHA?
To restore the ability of the blood to carry oxygen by administering a blood transfusion.
How are defects of primary hemostasis characterized?
By hemorrhages.
What can cause severe anemia in dogs with defects of primary hemostasis?
Hemorrhages from surface capillaries in the gastrointestinal tract.
What are the common sites for surface hemorrhages on the skin?
Oral mucous membranes, inguinum and axillae, and on the concave surface of the pinnae.
How is thrombocytopenia diagnosed?
By complete blood cell count or examination of a fresh blood smear.
What can prolong the Buccal Mucosal Bleeding Test (BMBT)?
Disturbance of the platelet plug as it forms or a platelet function defect.
At what value does thrombocytopaenia refer to a reduction in the normal platelet count?
Approximately 150x109/l, but spontaneous hemorrhage is unlikely unless the count drops below 30-50x109/l.
What does a diagnosis of SLE rely on?
A diagnosis of SLE relies on confirming the presence of more than 1 immunological syndrome and a positive titre in an ANA test or detection of LE cells.
What does the ANA test provide evidence of?
The ANA test provides evidence of antibodies directed against nuclear antigens.
What is the method used to perform the ANA test?
The ANA test is performed by adding the patient serum to cells, usually sections of normal rat liver.
What is the diagnostic significance of the homogenous pattern in the ANA test?
The homogenous pattern is apparently associated with more severe, multi-systemic signs.
What does a high titre result in the ANA test indicate?
A high titre result (>1:640) in the ANA test indicates that more antibodies are present and provides a more robust diagnosis of SLE.
What are LE cells?
LE cells are phagocytes (neutrophils or macrophages) that have ingested entire nuclei.
What is the suggested investigation for dogs with suspected SLE?
Recommended investigations for dogs with suspected SLE would include tests to confirm the diagnosis, examination of a blood smear, or DAT, or detection of agglutination in saline, aspirates from effused joints, and submission of blood for the ANA titre.
Why is it important to determine the severity and the number of affected body systems in SLE?
It is important to determine the severity and the number of affected body systems in SLE because it may lead to a decision for euthanasia rather than attempting treatment due to the relatively poor prognosis of the disease.
What complications are dogs with IMHA at high risk of?
Thromboembolic complications
What are possible risk factors for the hypercoagulable state in dogs with IMHA?
Release of pro-thrombotic substances, effects of inflammatory cytokines, activation of platelets and vascular endothelial cells, and development of a DIC-like state
What is the cause of the regenerative response in dogs with IMHA?
Decreased oxygen carriage in blood causing hypoxia in the kidneys, leading to the release of erythropoietin (EPO)
What is the most common leukogram seen in dogs with IMHA?
Inflammatory leukogram consisting of neutrophilia and monocytosis
What is the syndrome called when dogs with IMHA have extremely low platelet counts?
Evan’s syndrome (ITP and IMHA)
What organ dysfunction may be caused by decreased oxygen carriage in the blood?
Mild azotaemia and increased hepatocellular enzyme activities
What type of bilirubin is likely to be increased in dogs with IMHA?
Unconjugated bilirubin
What is a potential complication of IMHA rarely encountered in dogs?
Azotaemia due to the excretion of large amounts of haemoglobin through the kidneys
What can be used to determine the severity of proteinuria in dogs?
Urine protein: creatinine ratio
In addition to proteinuria, what other tests should be considered to determine the underlying cause of immune-mediated disease in dogs?
Imaging of the thorax and abdomen and testing for relevant infectious disease agents
What is the potential cause of a syndrome resembling SLE in dogs treated with penicillamine?
Treatment with penicillamine
In cats, what medication has been associated with a SLE-like syndrome?
Propylthiouracil
What is the new name for Shar Pei fever in veterinary medicine?
Shar Pei Autoinflammatory Disease (SPAID)
What is the suggested underlying cause of SPAID in Shar Pei dogs?
Mutation in a gene encoding an anti-inflammatory protein (MTBP)
Which pro-inflammatory cytokine is increased in the blood of dogs with SPAID?
Interleukin 6 (IL-6)
What is one of the acute phase proteins induced by IL-6?
Serum amyloid A (SAA)
What does rheumatoid factor (RF) refer to?
IgM antibodies in the serum that are specific for other antibodies
What can rheumatoid factor be used as?
Markers of the disease
How is the test for rheumatoid factor reported?
As a titre
What do high titres of rheumatoid factor indicate?
Large amounts of rheumatoid factor are present
What do low titres of rheumatoid factor indicate?
Only small amounts of rheumatoid factor are present
What is the classification system suggested for dogs with IMPA?
Type 1: No underlying cause detected. Type 2: Related to underlying bacterial infection. Type 3: Related to underlying gastrointestinal disease. Type 4: Related to underlying neoplasia
What does the production of immune complexes in the joints stimulate?
An inflammatory reaction
What additional tests should be performed to exclude the likely underlying causes of IMPA?
Complete blood count, biochemical profile, imaging of the thorax and abdomen, and infectious disease testing
How should the dose of prednisolone be increased to achieve a response to treatment in dogs with IMHA?
The dose of prednisolone should be increased to the initial dose that was used to achieve the response to treatment in dogs with IMHA.
What should be considered if there are repeated relapses when trying to taper the treatment in dogs with IMHA?
In a very small number of dogs, it may be necessary to continue with lifelong immunosuppressive treatment at a low dose if there are repeated relapses when trying to taper the treatment in dogs with IMHA.
What caution should be exercised if IVIG is administered to dogs with acute relapse of IMHA?
IVIG may be administered to produce a response to treatment again in dogs with acute relapse of IMHA, but caution should be exercised if it was administered previously due to the risk of allergic reactions.
What treatment option may be reasonable to consider for dogs with repeated relapses of IMHA?
For dogs with repeated relapses of IMHA, it may be reasonable to consider splenectomy, removing the macrophages that are principally responsible for the destruction of the red blood cells. This should ideally be conducted after all other options have been exhausted and when the dog is not receiving immunosuppressive or thromboprophylactic drugs.
How does the treatment of cats with IMHA differ from dogs?
Treatment of cats with IMHA follows similar principles to dogs but with a few important differences. The starting dose of the glucocorticoid should be higher in cats, typically 4 mg/kg per day of prednisolone or 0.4-0.6 mg/kg dexamethasone IV SID. Cats also appear to have a greater rate of relapse and may require lifelong treatment compared to dogs.
What are the most commonly used ‘second line’ immunosuppressive drugs in cats with IMHA?
The most commonly used ‘second line’ immunosuppressive drugs in cats with IMHA are ciclosporin and chlorambucil, with some reports of the safe use of mycophenolate mofetil.
What is the recommended initial therapy for dogs with ITP to achieve a response to treatment?
A high dose of prednisolone +/- one of the additional drugs (ciclosporin, azathioprine, or mycophenolate mofetil) is recommended as the initial therapy for dogs with ITP to achieve a response to treatment.
What treatment options have been shown to have no difference in survival for dogs with ITP?
A randomised, controlled trial showed that administration of a single dose of IVIG or vincristine early in treatment for dogs with ITP resulted in no difference in survival to discharge from the hospital, indicating that either treatment may be suitable.
What are the major mechanisms of glucocorticoids in modulating and suppressing the immune system?
Glucocorticoids decrease the production of inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-2. They also decrease the expression of Fc receptors on macrophages, which are involved in phagocytosis.
What are the major side effects and clinicopathological abnormalities expected with administration of glucocorticoids?
The side effects of glucocorticoids include polyuria, polydipsia, polyphagia, excessive panting, muscle wastage, weakness, and lethargy.
Why is the dose of glucocorticoid drugs usually gradually tapered before stopping?
The dose of glucocorticoid drugs is usually gradually tapered before stopping to ensure that endogenous production of cortisol is restored and to avoid causing iatrogenic hypoadrenocorticism.
What is the rationale behind tapering the dose of glucocorticoids?
The rationale behind tapering the dose of glucocorticoids is to prevent withdrawal of the drug leading to iatrogenic hypoadrenocorticism and to allow the restoration of endogenous production of cortisol.
What are the major mechanisms of azathioprine, chlorambucil, mycophenolate mofetil, and leflunomide in modulating and suppressing the immune system?
These drugs modulate and suppress the immune system by various mechanisms, which may include reducing the production of lymphocytes and interfering with DNA synthesis in rapidly dividing immune cells.
What are the major side effects and clinicopathological abnormalities expected with administration of azathioprine, chlorambucil, mycophenolate mofetil, and leflunomide?
The major side effects and clinicopathological abnormalities expected with administration of these drugs may include bone marrow suppression, gastrointestinal disturbances, hepatotoxicity, and increased risk of opportunistic infections.
What is the appropriate clinical approach to the initial treatment of immune-mediated hemolytic anemia (IMHA), immune-mediated thrombocytopenia (IMTP), immune-mediated polyarthritis (IMPA)/erosive arthritis, and systemic lupus erythematosus (SLE)?
The appropriate clinical approach to the initial treatment of IMHA, IMTP, IMPA/erosive arthritis, and SLE involves the use of glucocorticoids as the first-line therapy, followed by potential combination therapy with other immunosuppressive drugs.
What are the likely side effects associated with the treatment of immune-mediated diseases, and what recommended tests should be considered?
The likely side effects associated with the treatment of immune-mediated diseases include those associated with glucocorticoids, as well as potential side effects from other immunosuppressive drugs. Recommended tests may include monitoring of organ function, complete blood counts, and immunoglobulin levels.
What are some dermatological changes associated with glucocorticoid treatment in dogs?
Some dermatological changes associated with glucocorticoid treatment in dogs include thinning of the skin, formation of visible striae, development of symmetrical alopecia of the flanks, increased risk of pyoderma, and, rarely, calcinosis cutis.
Why is it important to strike a balance between control of the underlying disease and glucocorticoid-related side effects in dogs with immune-mediated diseases?
It is important to strike a balance between control of the underlying disease and glucocorticoid-related side effects in dogs with immune-mediated diseases because side effects of treatment are a frequently-cited reason for euthanasia among owners of dogs with immune-mediated diseases.
What is glucocorticoid resistance and how common is it in human patients?
Glucocorticoid resistance refers to the inability of glucocorticoid drugs to produce the typical immunomodulatory effects at standard dose rates. Approximately 30% of human patients are estimated to be ‘glucocorticoid resistant’.
What are some possible reasons for glucocorticoid resistance?
Possible reasons for glucocorticoid resistance include polymorphisms in the glucocorticoid receptor gene, alterations in the affinity of the drugs for the receptor, and variations in the expression of efflux pumps such as P glycoprotein.
Are there any tests available in veterinary medicine to determine if a dog is ‘glucocorticoid resistant’?
No, there are no tests available in veterinary medicine to determine whether dogs are ‘glucocorticoid resistant’. It may be suspected in cases that fail to show typical biochemical or haematological changes after administration of the drugs at standard dose rates.
What is the recommended initial dose rate of prednisolone for primary treatment of immune-mediated diseases in dogs?
The recommended initial dose rate of prednisolone for primary treatment of immune-mediated diseases in dogs is 2-3 mg/kg per day, either administered as a single daily dose or divided into 2 doses.
Why is it usually recommended to administer prednisolone with food?
It is usually recommended to administer prednisolone with food to minimize gastrointestinal side effects.
What is the usual starting dose of dexamethasone for treating immune-mediated diseases in dogs?
The usual starting dose of dexamethasone for treating immune-mediated diseases in dogs is 0.2-0.4 mg/kg, usually administered intravenously once daily.
What are the recommended treatment options for dogs with IMHA?
The recommended treatment options for dogs with IMHA include prednisolone at 2-4 mg/kg PO SID (if APPROPRIATE), dexamethasone at 0.2-0.4 mg/kg IV SID (if inappetent), and either azathioprine, ciclosporin, or mycophenolate mofetil as second-line drugs.
What is the starting dose of prednisolone for dogs with IMHA?
The starting dose of prednisolone for dogs with IMHA is 2-4 mg/kg per day.
What are the possible aspects to consider when determining if dogs with IMHA are responding to treatment?
The possible aspects to consider when determining if dogs with IMHA are responding to treatment include monitoring the red blood cell count (usually by packed cell volume or haematocrit), assessing the total bilirubin concentration, and looking at tests that indicate an immune-mediated cause of anaemia.
What are the signs that a dog with IMHA is responding to treatment?
The signs that a dog with IMHA is responding to treatment include a stable or increasing red blood cell count, a decrease in the total bilirubin concentration, resolution of agglutination (after saline dilution), and a decrease in the number of spherocytes.
What should be done if a dog with IMHA fails to respond to the initial treatment?
If a dog with IMHA fails to respond to the initial treatment, several options should be considered, starting with allowing enough time to see a response. It is important to realize and warn the owners that it may take 5 days or more to see a response to treatment, even when the selected treatment is appropriate.
What are the second-line drugs that can be used for dogs with IMHA?
The second-line drugs that can be used for dogs with IMHA include azathioprine, ciclosporin, and mycophenolate mofetil.
What is the expected timeframe to see a response to treatment in dogs with IMHA?
It may take 5 days or more to see a response to treatment in dogs with IMHA.
What are the parameters to monitor when assessing a dog’s response to treatment for IMHA?
The parameters to monitor when assessing a dog’s response to treatment for IMHA include the red blood cell count (usually by packed cell volume or haematocrit), total bilirubin concentration, agglutination (after saline dilution), and the number of spherocytes.
What is the final product of the purification and quality control steps in the preparation of intravenous immunoglobulin (IVIG)?
The final product of the purification and quality control steps in the preparation of IVIG is a mixture of antibodies with specificity to many different antigens.
What are some immune-mediated and autoimmune diseases in people that can be treated with IVIG?
Some immune-mediated and autoimmune diseases in people that can be treated with IVIG include myasthenia gravis, immune thrombocytopenia, and some neurological diseases.
What is one suggested mechanism of action of IVIG?
IVIG is suggested to occupy the Fc receptors on the surface of macrophages and neutrophils, preventing the phagocytosis of targets that have been opsonised by antibodies.
What is the recommended dosage for IVIG in dogs?
The recommended dosage for IVIG in dogs is 0.5-1 gram/kg, administered as a single infusion over 4-6 hours.
What are the potential risks associated with IVIG administration?
The potential risks associated with IVIG administration include the risk of allergic reactions due to the presence of foreign proteins. Careful monitoring and the administration of antihistamines are recommended to reduce this risk.
What is the initial treatment of choice for immune-mediated diseases in dogs and cats?
The initial treatment of choice for immune-mediated diseases in dogs and cats is prednisolone (or dexamethasone if not able to tolerate oral medications).
What are some possible combinations of prednisolone with other immunosuppressive drugs?
Some possible combinations of prednisolone with other immunosuppressive drugs include prednisolone + azathioprine or mycophenolate mofetil, prednisolone + ciclosporin, and prednisolone + leflunomide.
What is the recommended daily limit for the dose of prednisolone when starting 2 different drugs from the outset?
The recommended daily limit for the dose of prednisolone when starting 2 different drugs from the outset is 2 mg/kg per day.
Why is the administration of ketoconazole no longer recommended with ciclosporin?
The administration of ketoconazole is no longer recommended with ciclosporin because it may result in unpredictable pharmacokinetics for ciclosporin and because ketoconazole is associated with a number of other side effects.
What is the increased risk associated with ciclosporin?
Ciclosporin increases the risk of opportunistic infections.
What type of fungal infections have been reported in dogs receiving ciclosporin with glucocorticoids?
Cutaneous fungal infections have been reported in dogs receiving ciclosporin with glucocorticoids.
How does ciclosporin affect Toxoplasma gondii in cats?
Ciclosporin has been identified as a risk factor for reactivation of Toxoplasma gondii in cats.
What are the potential health issues caused by the reactivation of Toxoplasma gondii?
Reactivation of Toxoplasma gondii may cause meningitis, hepatitis, pancreatitis, and interstitial pneumonia.
Why do many clinicians recommend measuring anti-Toxoplasma antibodies in serum before starting treatment with ciclosporin?
Many clinicians recommend measuring anti-Toxoplasma antibodies in serum before starting treatment with ciclosporin to assess the risk of reactivation of Toxoplasma gondii.
What is the purpose of using ciclosporin as the sole drug in treatment?
Ciclosporin can be used as the sole drug in treatment for patients that might not tolerate prednisolone, such as dogs and cats with diabetes mellitus.
What is the recommended approach for tapering the dose of ciclosporin after stopping prednisolone?
When prednisolone has been stopped, the dose of ciclosporin may be tapered over several weeks-months, or it may be continued at the same dose for a fixed period of time, normally 6-8 weeks, then stopped without tapering.
Why is it important to administer drugs intravenously to severely affected dogs with IMHA?
Drugs should be administered intravenously to ensure they reach a therapeutic concentration in severely affected dogs with IMHA, as these dogs are often recumbent and inappetent.
What is the recommended route of administration for drugs that are only available orally in dogs with IMHA?
For drugs that are only available orally in dogs with IMHA, they should be tableted rather than put into food to ensure they are swallowed.
When should IVIG be considered for dogs refractory to treatment after 5-7 days?
IVIG should be considered for dogs refractory to treatment after 5-7 days, or when a response is not achieved with the initial treatment.
Why is thromboprophylaxis recommended for dogs with IMHA?
Thromboprophylaxis is recommended for dogs with IMHA because they are at high risk of thromboembolic complications due to the hypercoagulable state caused by the disease.
What are some thromboprophylactic drugs that can be administered to dogs with IMHA?
Thromboprophylactic drugs that can be administered to dogs with IMHA include unfractionated or low molecular weight heparins, clopidogrel, and aspirin.
What is the recommended approach for long-term treatment of dogs with IMHA?
Once the initial response is established, the starting doses of the immunosuppressive drugs are typically maintained for 2-3 weeks. If the dog is improving or stable, the prednisolone dose can be decreased gradually, with further reductions made approximately every 3 weeks if the dog continues to make good progress.
What should be monitored when using azathioprine in combination with prednisolone in dogs with IMHA?
Periodic biochemical profiles should be assessed to monitor for hepatotoxicity when using azathioprine in combination with prednisolone in dogs with IMHA.
What is the usual approach when a relapse occurs in dogs with IMHA?
When a relapse occurs in dogs with IMHA, usually while the prednisolone dose is being decreased, the usual approach involves re-evaluating the treatment and adjusting the medication accordingly.
What is the mechanism of action of leflunomide?
Leflunomide inhibits the enzyme dihydro-orotate reductase and prevents the synthesis of pyrimidine molecules (thymine and cytosine).
Why is leflunomide used in dogs?
Leflunomide is used to treat immune-mediated diseases in dogs due to its relatively good tolerance and effectiveness.
What is the recommended dose of leflunomide for immune-mediated diseases in dogs?
Recent evidence suggests a dose of 2 mg/kg PO SID (per day) is just as effective as the previously recommended dose of 3-4 mg/kg PO SID.
What are the reported side effects of leflunomide in dogs?
Leflunomide may cause lethargy, inappetence, vomiting, diarrhea, and hepatotoxicity in dogs. It can also cause cutaneous drug reactions and lung pathology in people.
What is the mechanism of action of alkylating agents like chlorambucil and cyclophosphamide?
Alkylating agents donate alkyl groups to nucleotides of DNA, causing breakage of the DNA strand and impaired DNA replication.
For what condition is chlorambucil commonly used in cats?
Chlorambucil is used in cats with immune-mediated diseases, especially IMHA (immune-mediated hemolytic anemia), in combination with prednisolone.
Why is cyclophosphamide no longer recommended for the treatment of dogs with IMHA?
Cyclophosphamide offered no additional advantage over prednisone alone in one clinical trial and was later associated with a poorer outcome in another study. It is also associated with more severe and long-lasting adverse effects.
What is the major concern with the use of alkylating agents?
The major concern with the use of alkylating agents is myelosuppression, which can cause a reduction in neutrophil count and bone marrow suppression.
How is the dose of prednisolone typically decreased in dogs?
The dose of prednisolone is typically decreased by 25-33% every 3 weeks in dogs.
What should be checked before each dose reduction in dogs with IMHA or ITP?
A complete blood cell count should be checked before each dose reduction in dogs with IMHA or ITP.
What should be checked at each dose reduction interval for dogs with IMPA?
The joints should be carefully palpated at each dose reduction interval for dogs with IMPA.
At what point is it safe to stop treatment with prednisolone in dogs?
It is safe to stop treatment with prednisolone once the dose has been decreased to 0.25 mg/kg every other day or lower, provided there has been no recurrence of disease while treating at this low dose.
What is advisable to consider periodically when monitoring glucocorticoid treatment in dogs?
It is advisable to consider periodic urine sampling (by cystocentesis) to check for possible urinary tract infection when monitoring glucocorticoid treatment in dogs.
What is the starting dose of prednisolone in cats?
The starting dose of prednisolone in cats is 4 mg/kg per day.
What can high doses of prednisolone in cats cause?
High doses of prednisolone in cats can cause sodium retention, expanding the extracellular fluid volume and causing volume overload.
What side effect occurs more commonly in cats receiving glucocorticoids than in dogs?
Diabetes mellitus occurs more commonly in cats receiving glucocorticoids than in dogs.
Why is the approach of combining immunosuppressive drugs adopted?
The approach of combining immunosuppressive drugs is adopted to allow for a lower dose of prednisolone to be used or to decrease the dose of prednisolone more quickly or in larger increments.
What are the potential risks of combining immunosuppressive drugs with different mechanisms of action?
Combining immunosuppressive drugs with different mechanisms of action may increase the risk of opportunistic infections or result in unpredictable drug interactions that alter the efficacy of the therapy.
What is the mechanism of action of ciclosporin?
Ciclosporin binds to proteins called cyclophilins in the cytoplasm of target cells, forming a complex that inhibits calcineurin, a calcium-dependent phosphatase.
Which transcription factor is normally activated by calcineurin?
Calcineurin normally activates the transcription factor NFAT (nuclear factor of activated T cells).
What is the effect of ciclosporin on cytokine production?
Ciclosporin decreases the production of interleukin-2 (IL-2) and other pro-inflammatory cytokines.
Why is it preferable to administer ciclosporin on an empty stomach?
Ciclosporin is poorly absorbed across the gastrointestinal tract, and its absorption is further impaired if it is administered with food.
What is pharmacodynamic monitoring for the effects of ciclosporin?
Pharmacodynamic monitoring involves measuring an effect of the drug, such as the expression of the IL-2 gene in blood, to determine if the desired effect is being achieved.
What is the most common side effect of ciclosporin?
The most common side effect of ciclosporin is vomiting and diarrhea, which are usually acute and self-limiting.
What is the dosing interval for azathioprine after the first 2-3 weeks of treatment?
Every other day
Why is the dosing interval of azathioprine increased after the first 2-3 weeks of treatment?
To reduce the risk of adverse effects
What is the recommended dose of mycophenolate mofetil?
10 mg/kg PO BID
What is the more recent evidence suggesting a lower effective dose of mycophenolate mofetil?
7-8 mg/kg PO BID
What are the common adverse effects associated with azathioprine?
Idiosyncratic hepatotoxicity, pancreatitis, and myelosuppression
What adverse effect is commonly associated with mycophenolate mofetil?
Acute gastrointestinal disease (vomiting and diarrhea)
Why is it important to monitor complete blood cell counts and biochemical profiles in dogs receiving azathioprine?
To monitor for possible adverse effects
Why is the use of azathioprine not recommended for cats?
Because they develop severe myelosuppression and other side effects at very low doses
What could be an alternative option for dogs that would not tolerate prednisolone?
Ciclosporin
What is often necessary to consider in cases of erosive arthritis?
Surgical stabilisation procedures
What is pancarpal arthrodesis used for?
Stabilising affected joints and allowing acceptable mobility
What is the recommended approach for treating Systemic Lupus Erythematosus (SLE)?
Using a second immunosuppressive drug in addition to the initial treatment
What should be done before increasing or re-starting treatment for relapses?
Checking if an underlying cause of immune-mediated disease was overlooked
What might be a reason for euthanasia of some cases with immune-mediated diseases?
Severe side effects of immunosuppressive drugs
In some cases, what might be confused with the disease itself?
Side effects of treatment
What should be considered when decreasing the dose of glucocorticoids during treatment?
A pragmatic approach and careful monitoring
What may be seen on a blood smear shortly before a sudden and dramatic increase in platelet count?
A small number of very large macroplatelets
At what platelet count does the risk of spontaneous haemorrhage decrease significantly?
Above 50x109/l
How long does it typically take for cutaneous haemorrhages to resolve once the platelet count improves above 50x109/l?
Few days
What is the approach to relapse in dogs with ITP?
The same as for IMHA
What happens once the platelet count starts to return to normal in people and dogs with ITP?
A hypercoagulable state develops
Why is thromboprophylactic treatment not administered when the platelet count is low?
It would increase the risk of spontaneous bleeding
What is the initial immunosuppressive treatment for dogs with IMPA?
As described for IMHA and ITP
What is a technique to assess continued response to treatment in dogs with muscle weakness related to prednisolone?
Repeated sampling of the joints for analysis of the synovial fluid
