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Immune-mediated Disorders Flashcards

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1
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A
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2
Q

What are immune-mediated disorders?

A

Disorders where the protective immune response is activated inappropriately, causing organ or cellular injury.

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3
Q

What is autoimmunity?

A

A condition characterized by a specific humoral or cell-mediated immune response against constituents of the body’s own tissues.

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4
Q

Define primary autoimmune disease.

A

Disorders in which no underlying cause can be identified, believed to result from immune system dysfunction or imbalance.

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5
Q

What is secondary autoimmunity?

A

Immune-mediated disorders with an identifiable underlying reason for the autoimmune response.

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6
Q

List examples of secondary causes of autoimmunity.

A
  • Infection
  • Exposure to certain drugs or toxins
  • Neoplasia
  • Vaccine administration
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7
Q

What are the four major mechanisms of hypersensitivity reactions?

A
  • Type I (immediate)
  • Type II (cytotoxic)
  • Type III (immune complex)
  • Type IV (delayed-type)
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8
Q

What is Type I hypersensitivity?

A

Involves IgE and mast cells, leading to activation of T-helper lymphocytes and B-cell differentiation to plasma cells.

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9
Q

What are the consequences of mast cell degranulation in Type I hypersensitivity?

A
  • Vasodilation
  • Edema
  • Eosinophil chemotaxis
  • Pruritus
  • Bronchoconstriction
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10
Q

Give examples of diseases mediated by Type I hypersensitivity.

A
  • Allergic bronchitis
  • Acute anaphylactic reactions
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11
Q

What characterizes Type II hypersensitivity?

A

Binding of antibodies (IgG or IgM) to specific molecules on cell surfaces, leading to cell destruction.

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12
Q

List classic examples of diseases mediated by Type II mechanisms.

A
  • Immune-mediated hemolytic anemia
  • Immune-mediated thrombocytopenia
  • Pemphigus foliaceous
  • Myasthenia gravis
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13
Q

What is Type III hypersensitivity?

A

Involves formation and deposition of soluble immune complexes within tissues, leading to localized inflammatory responses.

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14
Q

Give examples of diseases mediated by Type III hypersensitivity.

A
  • Feline infectious peritonitis
  • Glomerulonephritis
  • Systemic lupus erythematosus (SLE)
  • Rheumatoid arthritis
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15
Q

What defines Type IV hypersensitivity?

A

Involves cell-mediated immune response with activation of sensitized T cells and cytokine release.

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16
Q

List examples of diseases mediated by Type IV immune responses.

A
  • Leishmaniasis
  • Contact hypersensitivity
  • Polymyositis
  • Immune-mediated thyroiditis
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17
Q

What mechanisms prevent self-reactive B and T lymphocytes from maturing?

A
  • Deletion during thymus maturation
  • Peripheral deletion by apoptosis
  • Anergy in peripheral circulation
  • Suppression by regulatory T cells
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18
Q

What factors may lead to the loss of tolerance in autoimmunity?

A
  • Genetics
  • Environmental factors
  • Age
  • Hormonal influences
  • Other diseases affecting the immune system
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19
Q

How do genetics influence autoimmune diseases?

A

Certain breeds of dogs are at increased risk, and autoimmunity is reported more commonly in some families.

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20
Q

What environmental factors may contribute to the development of autoimmunity?

A
  • Exposure to infectious agents
  • Environmental toxins
  • Drug exposure
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21
Q

What is molecular mimicry in the context of autoimmunity?

A

A mechanism where infectious agents resemble self-antigens, potentially inducing an autoimmune response.

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22
Q

What role does vaccination play in autoimmunity?

A

The evidence is unclear and primarily anecdotal, making it difficult to establish a cause-and-effect relationship.

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23
Q

Which organ systems are commonly involved in immune-mediated diseases?

A
  • Joints
  • Skin
  • Kidney
  • Hematologic system
  • Eye
  • Neurologic system
  • Gastrointestinal tract
  • Respiratory tract
  • Endocrine glands
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24
Q

What is systemic lupus erythematosus (SLE)?

A

An autoimmune disorder that can involve multiple organ systems.

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25
What is the typical presentation of systemic immune-mediated disorders in dogs?
Dogs frequently present with one manifestation of the disorder and may later relapse with another.
26
What is the first step in the diagnostic approach for suspected immune-mediated disease in dogs or cats?
Obtain a complete history, including environmental or drug exposures, previous medical history, exposure to infectious agents, and vaccination history
27
What should be included in a typical minimal database for diagnosing immune-mediated disease?
* Complete blood count (CBC) * Serum biochemical profile * Urinalysis
28
Why is it important to rule out infectious agents as the primary cause of clinical signs in immune-mediated diseases?
Many immune-mediated diseases are characterized by fever and leukocytosis
29
What diagnostic tests are important for evaluating immune-mediated disease?
* Bacterial culture of urine and blood * Testing for common viral pathogens * Diagnostic imaging (thoracic and abdominal radiographs, abdominal ultrasonography)
30
What should be investigated after ruling out infection in the diagnostic evaluation for immune-mediated disease?
Chronic inflammatory and neoplastic causes
31
What specific tests of immune dysfunction may be indicated after excluding infectious and neoplastic diseases?
* Direct antiglobulin (Coombs) test for regenerative anemia * Test for rheumatoid factor (RF) for erosive polyarthritis
32
What is the purpose of the slide agglutination test?
To detect the presence of spontaneous agglutination of red blood cells (RBCs)
33
What causes spontaneous agglutination in red blood cells?
Presence of high-titer immunoglobulin (Ig) G or IgM on the RBC membrane
34
What is the main distinction that must be made when evaluating for agglutination?
Distinguishing agglutination from rouleaux formation
35
At what temperature should the slide agglutination test be evaluated?
As close to 37° C as possible
36
What does a positive slide agglutination test indicate?
The presence of surface-associated antibodies
37
What is the function of the direct Coombs test?
To detect the presence of antibody and/or complement bound to patient RBC membranes for diagnosing IMHA
38
What type of blood is used for the direct Coombs test?
Ethylenediamine tetraacetic acid (EDTA) anticoagulated blood
39
What reagents are typically used in the direct Coombs test?
Anti–dog antiglobulin antibody or anti–cat antiglobulin antibody produced in a different species
40
What is the significance of agglutination in the direct Coombs test?
Agglutination indicates that more than approximately 100 IgG antibody or C3 molecules are bound to the RBCs
41
What modifications can improve the diagnostic performance of the Coombs test?
* Use of monospecific antisera * More dilutions of reagents to avoid prozone effect * Testing at 4° C
42
What is the prozone effect in the context of the Coombs test?
A lack of reactivity observed with high concentrations of antibody
43
What is a potential limitation of the direct Coombs test results?
Both false-positive and false-negative results may occur
44
What should be considered when interpreting the results of the Coombs test?
Results should be interpreted in the context of clinical and hematologic data
45
What is the significance of a positive Coombs test in dogs with IMHA?
It does not distinguish primary from secondary IMHA ## Footnote A positive Coombs test indicates the presence of antibodies on RBCs but does not differentiate the type of IMHA.
46
What tests are used to detect antiplatelet antibodies in dogs and cats?
Flow cytometric techniques ## Footnote Tests for antiplatelet antibody include detection of platelet surface–associated IgG and serum platelet bindable antibody.
47
What is the sensitivity of the direct assay for platelet surface–associated antibodies in dogs with ITP?
Greater than 90% ## Footnote A negative result for platelet surface–associated antibody makes a diagnosis of ITP unlikely.
48
What is the purpose of measuring antinuclear antibodies (ANA) in dogs and cats?
Evaluation of suspected systemic lupus erythematosus (SLE) ## Footnote ANA are heterogenous antibodies directed against nuclear antigens.
49
How are antinuclear antibodies typically detected?
Immunofluorescent staining of frozen sections of rat liver or human epithelial cell lines ## Footnote Results are reported as a titer that reflects the highest dilution causing immunofluorescent staining.
50
What percentage of dogs with SLE have a positive ANA titer?
100% in one study ## Footnote Most cases had a titer greater than 1:256, correlating with disease severity.
51
What is the lupus erythematosus (LE) test used for?
It is a specific test for systemic lupus erythematosus (SLE) ## Footnote LE cells are neutrophils containing phagocytosed nuclear material.
52
What is the primary limitation of the LE test compared to the ANA test?
Lack of sensitivity ## Footnote The ANA test is more sensitive and less time-consuming, making it more commonly used.
53
What does the rheumatoid factor (RF) test detect?
Antibody directed against an individual's own IgG ## Footnote RF is used as one of the diagnostic criteria for rheumatoid arthritis.
54
What is the sensitivity range for RF in dogs with rheumatoid arthritis?
40% to 75% ## Footnote A negative titer does not rule out the disease.
55
What is C-reactive protein (CRP) a marker for?
Nonspecific acute-phase response to inflammation ## Footnote CRP is produced by hepatocytes and is a sensitive biomarker of inflammation.
56
In what conditions might CRP concentrations be increased in dogs and cats?
* Sepsis * Pancreatitis * IMHA * Inflammatory bowel disease * Rickettsial diseases * Chronic valvular disease * Certain neoplasia ## Footnote CRP is not specific for immune-mediated diseases but is useful for monitoring treatment response.
57
How does CRP concentration change in dogs with primary IMHA in response to treatment?
Decreases with immune-suppressive treatment ## Footnote CRP is not useful for predicting outcome or survival in primary IMHA.
58
What are the techniques used to detect antibodies in fixed tissues for immune-mediated diseases?
Immunofluorescence and immunoperoxidase techniques ## Footnote These techniques can visualize the presence of antibodies in tissue samples.
59
What is included in an autoimmune panel typically offered by laboratories?
* CBC * Platelet count * Coombs test * ANA * RF ## Footnote The significance of positive tests may be difficult to determine in patients where tests were not indicated.
60
What is a key consideration for clinicians regarding autoimmune panels?
Pick individual tests rather than automatically choosing a panel ## Footnote Some tests can be positive in dogs and cats with infectious diseases.
61
What are immunosuppressive drugs primarily used for?
Treatment for patients with immune-mediated disease ## Footnote It is crucial to identify and treat any underlying disease for a good response.
62
What is the aim of treatment for immune-mediated diseases?
Control the immune-mediated process while minimizing adverse effects of drugs ## Footnote Short-term adverse effects may need to be tolerated to achieve remission.
63
Why is it important to taper medications in long-term management?
To minimize adverse effects ## Footnote Tapering should be individualized based on the underlying disease, concurrent illness, and patient sensitivity.
64
What is a critical monitoring parameter in immune-mediated hemolytic anemia (IMHA)?
Complete blood count (CBC), reticulocyte count, and Coombs test ## Footnote Monitoring is essential before dose reduction.
65
In dogs with immune-mediated polyarthritis, what monitoring may be necessary before dose reduction?
Repeated joint taps for synovial fluid analysis ## Footnote This helps assess the response to treatment.
66
True or False: There is a wide interpatient variability in sensitivity to immunosuppressive drugs.
True ## Footnote Particularly notable with glucocorticoids.
67
What are common complications to monitor for in patients receiving glucocorticoids?
Gastrointestinal hemorrhage, hepatotoxicity, bone marrow suppression ## Footnote These complications can improve long-term outcomes when detected early.
68
What is the first-line treatment for most immune-mediated diseases?
Glucocorticoids ## Footnote They are chosen for their rapid action, broad effects, low immediate toxicity, and low cost.
69
What are exceptions to the use of glucocorticoids as first-line therapy?
Myasthenia gravis and immune-mediated polyarthritis ## Footnote In these cases, glucocorticoid treatment is avoided.
70
What factors may indicate the need for additional immunosuppressive drugs at the start of treatment?
Negative response to glucocorticoids alone ## Footnote Examples include canine Evans syndrome and systemic lupus erythematosus.
71
What common adjunctive immunosuppressive medications interfere with nucleotide synthesis?
* Azathioprine * Mycophenolate * Leflunomide ## Footnote These are used in conjunction with glucocorticoids.
72
What is azathioprine and its primary mechanism of action?
A thiopurine antimetabolite that inhibits DNA and RNA synthesis ## Footnote It decreases proliferation of rapidly dividing cells such as lymphocytes.
73
What are some potential adverse effects of azathioprine?
* Bone marrow suppression * Gastrointestinal upset * Pancreatitis * Hepatotoxicity ## Footnote Life-threatening myelosuppression can occur in a small percentage of patients.
74
What is the role of thiopurine methyltransferase (TPMT) in azathioprine metabolism?
It influences the metabolism of 6-mercaptopurine and its metabolites ## Footnote Variability in TPMT activity correlates with clinical outcomes.
75
What is the typical starting dose of azathioprine for dogs?
2 mg/kg PO q24h ## Footnote This dose is generally well tolerated.
76
What glucocorticoids are typically used in veterinary medicine?
* Hydrocortisone * Prednisone * Prednisolone * Methylprednisolone * Dexamethasone * Triamcinolone ## Footnote These vary according to duration, potency, and route of administration.
77
What is the ideal route of glucocorticoid administration in most patients?
Oral ## Footnote Intravenous administration may be necessary in cases of vomiting or absorption issues.
78
What is a strategy to minimize adverse effects of glucocorticoid therapy?
* Use the lowest dose possible * Switch to alternate-day therapy * Start with high doses and taper slowly ## Footnote Tapering should be based on objective measures of response.
79
What is azathioprine commonly used for?
Second-line drug in immune-mediated diseases such as IMHA, ITP, immune-mediated polyarthritis, inflammatory bowel disease, and SLE ## Footnote See Chapter 73 for specific indications for each of these diseases.
80
What is the typical starting dose of azathioprine for dogs?
2 mg/kg PO q24h
81
What are some common adverse effects of azathioprine?
Bone marrow suppression, gastrointestinal upset, pancreatitis, hepatotoxicity ## Footnote Adverse effects are uncommon.
82
What life-threatening condition can occur in a small percentage of dogs treated with azathioprine?
Myelosuppression
83
What are the characteristics of myelosuppression caused by azathioprine?
Neutropenia, thrombocytopenia, sometimes anemia
84
How common is hepatotoxicity in dogs treated with azathioprine?
Occurs in approximately 15% of dogs within 14 to 21 days after initiation of therapy
85
Which breed of dog is over-represented in experiencing hepatotoxicity from azathioprine?
German Shepherds
86
When does bone marrow suppression typically occur after starting azathioprine therapy?
Within 1 to 4 months
87
How long does it typically take for bone marrow suppression to be reversible after discontinuation of azathioprine?
7 to 14 days
88
How often should dogs receiving azathioprine have a CBC evaluated and hepatic enzyme activities measured during the first month of treatment?
Every 1 to 2 weeks
89
What should be considered for dogs showing evidence of myelosuppression at the typical dose of azathioprine?
Lower doses of azathioprine (2 mg/kg PO q48h)
90
What has preliminary studies of TPMT activity in dogs shown?
Not useful in predicting adverse reactions from azathioprine
91
Which breeds of dogs have decreased and increased TPMT activity respectively?
Decreased TPMT activity: Giant Schnauzers; Increased TPMT activity: Alaskan Malamutes
92
Is azathioprine recommended for use in cats?
No, severe neutropenia and thrombocytopenia can occur even at reduced doses
93
With which medication is azathioprine typically used in conjunction?
Immunosuppressive doses of prednisone
94
What should be done if a positive response is observed to combined therapy of azathioprine and prednisone?
Taper the prednisone dose over 2 to 4 months
95
What is the initial change in dosing schedule for azathioprine if complete discontinuation of prednisone is possible?
Change to every other day and then to every third day before complete cessation
96
How long can bone marrow suppression be reported after starting azathioprine treatment?
As long as 12 months
97
What is Chlorambucil (Leukeran)?
An alkylating agent used to treat lymphoid neoplasms and immune-mediated disease. ## Footnote Chlorambucil is a prodrug metabolized to phenylacetic acid mustard.
98
What is the usual starting dose of Chlorambucil for immune-mediated diseases in dogs and cats?
0.1 to 0.2 mg/kg PO q24h. ## Footnote This dosage is commonly used for treating immune-mediated conditions.
99
What are the common adverse effects of Chlorambucil?
Bone marrow suppression, gastrointestinal upset, predisposition to infection. ## Footnote These effects can impact the health of treated animals.
100
What is Cyclosporine?
A potent immunomodulating agent, cyclic polypeptide extracted from fungi. ## Footnote It inhibits the initial activation phase of CD4 T lymphocytes.
101
How does Cyclosporine affect T lymphocytes?
It blocks the transcription of genes encoding cytokines, particularly IL-2, preventing T lymphocyte activation and proliferation. ## Footnote This helps manage immune-mediated diseases.
102
What is the treatment of choice for perianal fistulas in dogs?
Cyclosporine. ## Footnote It is also used for various immune-mediated diseases.
103
What is the recommended dosage range for Cyclosporine?
5 mg/kg q24h to 10 mg/kg PO q12h. ## Footnote Dosage varies based on the product used and the disease treated.
104
What are some adverse effects of Cyclosporine in dogs?
Gastrointestinal disturbance, predisposition to infection, gingival hyperplasia, papillomatosis, increased shedding. ## Footnote A dermatosis from atypical staphylococcal infection has also been reported.
105
What is Leflunomide and its mechanism of action?
A drug that inhibits pyrimidine synthesis and tyrosine kinases involved in cell differentiation and signal transduction. ## Footnote It inhibits T- and B-cell proliferation and has anti-inflammatory effects.
106
What is the current recommended dose of Leflunomide in dogs?
2 to 4 mg/kg PO q24h. ## Footnote Monitoring through the Clinical Pharmacology Laboratory at Auburn University is available.
107
What is Mycophenolate Mofetil?
A prodrug of mycophenolic acid, an inhibitor of inosine monophosphate dehydrogenase (IMPDH). ## Footnote It inhibits B and T cell proliferation and decreases antibody production.
108
What is the common dosage for Mycophenolate Mofetil in dogs?
10 mg/kg PO q12h. ## Footnote Gastrointestinal toxicity is the most common adverse effect.
109
What is Splenectomy and its purpose?
An adjunctive therapy for managing hematologic immune-mediated diseases like IMHA and ITP. ## Footnote It aims to reduce phagocytosis of antibody-coated RBCs and platelets.
110
What are the potential risks of Splenectomy?
Hemorrhage, thromboembolic complications, impaired RBC regeneration. ## Footnote The spleen plays a role in extramedullary hematopoiesis.
111
What is Human Intravenous Immunoglobulin (hIVIG)?
A preparation of polyspecific IgG obtained from pooled plasma of healthy human blood donors. ## Footnote It is used to treat various immune-mediated diseases in dogs.
112
What are some mechanisms by which hIVIG modulates the immune system?
* Decreased production of autoantibodies * Functional modulation of T cells * Decreased natural killer cell activity * Blockade of complement-mediated cell damage * Modulation of proinflammatory cytokines. ## Footnote These mechanisms contribute to its therapeutic effects.
113
What are the risks associated with hIVIG treatment in dogs?
Potential for sensitization and anaphylaxis, increased risk of thromboembolism. ## Footnote Anaphylactic reactions have been reported but are rare.
114
What is Pentoxifylline?
A methylxanthine derivative that improves RBC deformability and has immunomodulating effects. ## Footnote It inhibits IL-1, IL-6, and tumor necrosis factor-α.
115
What is the recommended dosage of Pentoxifylline in dogs?
10 to 15 mg/kg PO q8h. ## Footnote This dosage is based on its pharmacokinetics in dogs.
116
What is the primary effect of pentoxifylline on red blood cells?
Improves deformability of RBCs ## Footnote The exact mechanisms of this improvement are unknown.
117
Which cytokines does pentoxifylline inhibit?
* IL-1 * IL-6 * Tumor necrosis factor-α ## Footnote These immunomodulating effects contribute to its therapeutic action.
118
What is the recommended dosage of pentoxifylline in dogs?
10 to 15 mg/kg PO q8h ## Footnote This dosage is based on pharmacokinetics described in dogs.
119
What immune-mediated diseases is pentoxifylline primarily used to manage in veterinary medicine?
* Cutaneous immune-mediated diseases * Dermatomyositis * SLE * Various forms of vasculitis ## Footnote Its efficacy in other immune-mediated diseases is not established.
120
What are some uncommon adverse effects of pentoxifylline in dogs?
* Vomiting * Diarrhea * Bone marrow suppression * Flushing ## Footnote These effects are not commonly observed.
121
What type of agent is vincristine?
Antineoplastic and immunosuppressive agent ## Footnote It is derived from the periwinkle plant.
122
What is the mechanism of action of vincristine related to platelets?
Binds to the microtubular structural protein tubulin ## Footnote Tubulin is abundant within platelets.
123
What happens to platelet numbers at low doses of vincristine?
Transient increase in circulating platelet numbers ## Footnote At higher doses, it can lead to myelosuppression and thrombocytopenia.
124
What is the major indication for vincristine in treating immune-mediated disease?
Adjunctive therapy for dogs with severe ITP ## Footnote It improves platelet count recovery compared to prednisone alone.
125
What is the administration route and dosage for vincristine in dogs?
0.02 mg/kg IV as a single dose ## Footnote This is used in conjunction with glucocorticoids.
126
What advantages does vincristine have over other treatments for ITP?
* Readily available * Inexpensive * Rapid increase in platelet number * Shorter duration of hospitalization ## Footnote Bone marrow suppression is not reported at the low dose used.
127
True or False: Bone marrow suppression has been reported at the low single dose of vincristine used for treatment of ITP.
False ## Footnote Bone marrow suppression may occur at higher doses, but not at the low dose.
128
What care should be taken during the intravenous administration of vincristine?
It is highly caustic if extravasation occurs ## Footnote Proper administration techniques are crucial to avoid complications.
129
What is immune-mediated hemolytic anemia (IMHA)?
A clinical syndrome where anemia results from accelerated destruction of red blood cells by immune-mediated mechanisms ## Footnote IMHA is the most common cause of hemolytic anemia in dogs but is uncommon in cats.
130
What are the two types of IMHA?
* Primary IMHA (true autoimmune hemolytic anemia) * Secondary IMHA ## Footnote Primary IMHA involves antibodies against RBC membrane antigens, while secondary IMHA has an underlying disease as a precipitating factor.
131
What are the common antibody classes identified on RBCs in IMHA?
* Immunoglobulin (Ig) G * IgM * IgA ## Footnote Complement is usually also present.
132
What is a potential cause of secondary IMHA?
* Infection * Neoplastic diseases * Exposure to certain drugs, venoms, and possibly vaccines ## Footnote Secondary IMHA may occur after exposure to various factors.
133
What breed is at the greatest risk for developing IMHA?
Cocker Spaniel ## Footnote The Cocker Spaniel accounts for as many as one third of cases.
134
What is the typical age range of dogs affected by primary IMHA?
1 to 13 years, with a median age of 6 years ## Footnote Females and neutered dogs appear more predisposed than intact males.
135
What is the median hematocrit level in dogs with IMHA?
13% ## Footnote The anemia in IMHA is typically moderate to marked.
136
What is autoagglutination?
The clumping of red blood cells due to the presence of antibodies ## Footnote It is considered definitive evidence of antibody-mediated RBC hemolysis.
137
What is the significance of spherocytes in IMHA?
They are considered a hallmark morphologic change and may be diagnostic for IMHA when present in sufficient numbers ## Footnote Spherocytes are formed by partial removal of antibody-coated RBC membranes.
138
What is the first-line treatment for hemolysis in dogs with IMHA?
High doses of glucocorticoids ## Footnote Prednisolone or prednisone at a dose of 2-4 mg/kg/day orally is preferred.
139
What is the typical response time for glucocorticoid treatment in IMHA?
Some improvement within the first 7 days, full effect in 2 to 4 weeks ## Footnote Indications of resolution include stabilization of hematocrit and normalization of the reticulocyte count.
140
What should be done if a dog with IMHA does not respond to glucocorticoids?
An additional immunosuppressive drug should be added to the treatment regimen ## Footnote This addresses cases where glucocorticoid treatment alone is insufficient.
141
What diagnostic tests are performed to confirm IMHA?
* Complete blood count (CBC) * Serum biochemistry panel * Urinalysis ## Footnote Further testing is directed at identifying antibodies against RBC membranes.
142
What is the role of the direct Coombs test in diagnosing IMHA?
It detects antibodies or complement on the RBC surface but is not specific for IMHA ## Footnote Approximately 60% to 80% of canine patients with IMHA have a positive Coombs test.
143
What are ghost cells?
Remnant membranes of RBCs that have undergone intravascular lysis ## Footnote Ghost cells are not diagnostic for IMHA as lysis can occur from various mechanisms.
144
What is the typical prognosis for dogs with IMHA?
Poor prognosis associated with the disease ## Footnote Serious complications such as pulmonary thromboembolism and DIC are common.
145
What factors influence the severity of hyperbilirubinemia in IMHA?
* Rate of hemolysis * Hepatic function ## Footnote Hepatic function may be compromised by hypoxia and hepatic necrosis.
146
What is the relationship between vaccination and IMHA?
Recent vaccination has been implicated in the pathogenesis of IMHA, but its importance remains unclear ## Footnote Studies have shown varying associations with IMHA development post-vaccination.
147
What is the typical duration of clinical signs before presentation in dogs with IMHA?
Median of 4 days ## Footnote Seasonal increases in diagnosis have been reported, particularly in warmer months.
148
What is thrombocytopenia, and how is it related to IMHA?
Decreased platelet count, often present in dogs with IMHA ## Footnote Proposed mechanisms include antibodies against platelets and RBCs, DIC, and splenic sequestration.
149
What is the significance of identifying secondary causes of IMHA?
Secondary causes may influence management strategy and prognosis ## Footnote A thorough diagnostic approach is essential to rule out these causes.
150
What is the advantage of starting adjunctive immunosuppressive drugs early in IMHA treatment?
No time is lost waiting to identify which patients will respond to glucocorticoid treatment alone. ## Footnote Most adjunctive immunosuppressive drugs take 2 to 4 weeks to have an appreciable effect on immune cells.
151
What are the disadvantages of early adjunctive immunosuppressive therapy?
Risks include adverse effects, cost, lack of evidence of benefit, and lack of consensus on second-line agents. ## Footnote A retrospective study found no benefit of azathioprine therapy in dogs treated with prednisolone.
152
What are the most common adjunctive immunosuppressive drugs used in canine IMHA?
* Azathioprine * Cyclosporine * Mycophenolate
153
When should adjunctive immunosuppressive medications be considered in dogs with IMHA?
In dogs that do not respond within 5 to 7 days of glucocorticoid treatment or require more than two blood transfusions. ## Footnote Also in dogs with poor tolerance of glucocorticoids or poor prognostic indicators.
154
What should be monitored when using azathioprine in IMHA treatment?
CBC and hepatic enzymes due to the risk of bone marrow suppression and hepatotoxicity.
155
What is the recommended dosing frequency for azathioprine after the initial treatment period?
Every other day after the first 2 weeks of daily administration.
156
What formulation of cyclosporine is most appropriate for veterinary patients?
Atopica®.
157
What cytokine is consistently increased in dogs with IMHA?
Interleukin-2 (IL-2).
158
What is the mechanism of action of mycophenolate mofetil (MMF)?
Similar to that of azathioprine.
159
What is a significant risk associated with using mycophenolate in dogs with IMHA?
Dose-dependent gastrointestinal toxicity, including severe hemorrhagic diarrhea.
160
What is the role of human intravenous immunoglobulin (hIVIG) in treating canine IMHA?
Anecdotal reports suggest positive responses, but controlled studies show no benefit when administered with glucocorticoids.
161
What is the ideal type of blood product for transfusion in dogs with severe IMHA?
Packed RBCs (pRBCs).
162
What factors should be considered when determining the need for blood transfusion in dogs with IMHA?
Severity, rate of onset, chronicity of anemia, and concurrent disease.
163
What is the recommended starting dose for heparin in dogs with IMHA?
200 to 300 U/kg subcutaneous (SC) q6h.
164
What are common complications associated with IMHA?
* Thromboembolic events (TEs) * Infection * Gastrointestinal ulceration * Iatrogenic hyperadrenocorticism
165
What is the prognosis for dogs with IMHA that respond rapidly to glucocorticoid treatment?
Good prognosis, with many able to discontinue medications after tapering.
166
What factors indicate a guarded prognosis in dogs with IMHA?
* Need for multiple drugs * Persistent autoagglutination * Azotemia * Elevated bilirubin concentration * Marked thrombocytopenia * Severe leukocytosis
167
What is the mortality rate range for dogs with primary IMHA?
26% to 70%.
168
What is the relationship between hypercoagulability and prognosis in dogs with IMHA?
Dogs that are hypercoagulable have a better prognosis than those with normal coagulability.
169
True or False: The prognosis for Cocker Spaniels with IMHA differs from that of other breeds.
False.
170
What is the median age of cats diagnosed with primary IMHA?
2 years
171
Which infections are commonly associated with secondary causes of antierythrocyte antibody formation in cats?
* Feline leukemia virus * Mycoplasma haemofelis
172
What type of anemia is primarily seen in cats with IMHA?
Nonregenerative anemia
173
What is the first-line treatment for most cats with IMHA?
Prednisolone alone
174
Which immunosuppressive drugs may be considered for cats needing additional treatment for IMHA?
* Chlorambucil * Cyclosporine * Mycophenolate
175
Why is azathioprine not recommended for cats with IMHA?
Risk of unacceptable adverse effects
176
What is PRCA characterized by?
Severe, nonregenerative anemia with marked depletion or absence of erythroid precursors
177
What laboratory finding can indicate concurrent peripheral hemolysis in PRCA?
Presence of spherocytes and a positive direct Coombs test
178
How is PRCA diagnosed?
Evaluation of a bone marrow aspirate and core biopsy
179
What is the prognosis for dogs with PRCA?
Better than for IMHA, with mortality less than 20%
180
What is the major cause of death in dogs with PRCA?
Euthanasia due to high cost of supportive care
181
What is aplastic anemia characterized by?
Cytopenia of all three marrow-derived cell lines and a hypocellular/acellular bone marrow
182
List some reported causes of aplastic anemia in dogs and cats.
* Infectious agents (Ehrlichia spp., parvovirus, etc.) * Hormonal (estrogens) * Drug associated * Radiation associated * Idiopathic
183
What is the prognosis for idiopathic aplastic anemia?
Generally guarded to poor
184
What is immune-mediated thrombocytopenia (ITP)?
Thrombocytopenia resulting from antibody-mediated accelerated destruction of platelets
185
What is the most common cause of severe thrombocytopenia in dogs?
Immune-mediated thrombocytopenia
186
What are common findings in dogs with primary ITP?
* Sudden onset of petechial and ecchymotic hemorrhages * Epistaxis * Hematochezia * Easy bruising
187
What is the typical age range for dogs diagnosed with primary ITP?
8 months to 15 years
188
What is the first-line treatment for immune-mediated thrombocytopenia?
High doses of corticosteroids
189
What is the first-line corticosteroid used for ITP treatment?
Prednisolone or prednisone
190
What is a potential complication of glucocorticoid treatment in cats?
Increased risk of diabetes mellitus
191
How are the bone marrow evaluations used in the management of PRCA?
To determine when to change the treatment protocol
192
What may indicate primary ITP during diagnosis?
Severe thrombocytopenia (<50,000 platelets/µL)
193
What is a notable feature of platelets in dogs with ITP?
Platelets are often larger and may be hemostatically more competent
194
What should be checked for in dogs suspected of having ITP?
Other causes of severe thrombocytopenia
195
What does a positive assay for platelet-bound antibody indicate?
Highly sensitive but not specific for a diagnosis of ITP
196
What is the significance of megakaryocytes in the bone marrow for dogs with ITP?
Normal to increased numbers are typically present
197
What is the role of doxycycline in the treatment of immune-mediated thrombocytopenia?
Concurrent treatment with immunosuppressive drugs
198
What are the key treatments for Immune Thrombocytopenia (ITP)?
Immunosuppressive drugs and doxycycline ## Footnote Doxycycline is often initiated concurrently due to potential delays in serology results.
199
What is the first line of treatment for ITP?
High doses of corticosteroids ## Footnote Corticosteroids block macrophage-mediated destruction of platelets.
200
What is the corticosteroid of choice for treating ITP in dogs?
Prednisolone or prednisone at 2-4 mg/kg/day PO
201
What is an acceptable alternative corticosteroid for dogs that do not tolerate oral glucocorticoids?
Dexamethasone (0.25-0.6 mg/kg IV q24h)
202
When should vincristine be considered in the treatment of ITP?
For dogs with severe ITP (platelet count < 15,000/µL) or active hemorrhage
203
What is the effect of vincristine on platelet count and hospitalization duration?
Increases platelet count more rapidly and shortens hospitalization duration
204
What did a prospective study find about hIVIG treatment in dogs with ITP?
Shortens platelet recovery time compared to glucocorticoids alone
205
What should be limited regarding the use of hIVIG in dogs with ITP?
Use should be limited to patients failing to respond to glucocorticoids and vincristine due to high cost
206
What is the median platelet recovery time for dogs treated with prednisone and either vincristine or hIVIG?
3 days (range 1-10 days)
207
How should the dose of prednisone be tapered?
Not more rapidly than 20% to 30% per month over 3 to 6 months
208
What should be done for dogs that do not respond to glucocorticoids and vincristine?
Bone marrow aspiration cytology and biopsy should be performed
209
What are appropriate adjunctive immunosuppressive medications for dogs with ITP?
* Azathioprine * Cyclosporine * Mycophenolate
210
Which adjunctive immunosuppressive medication is most commonly used at the authors' institution?
Azathioprine and mycophenolate
211
What was found about the survival of dogs on prednisolone with cyclosporine versus mycophenolate?
Survival was similar, but mycophenolate had fewer side effects and lower cost
212
What should be monitored before and after any change in immunosuppressive therapy?
Platelet count
213
What is an acceptable platelet count to maintain in dogs that cannot avoid severe glucocorticoid side effects?
Greater than 100,000 per µL
214
What supportive care is critical for dogs with ITP?
* Cage rest * Exercise restriction * Minimizing venipuncture
215
What blood products provide clinically significant platelet activity for transfusions?
* Fresh whole blood * Platelet-rich plasma * Platelet concentrate * Frozen platelet concentrate
216
What is the typical duration of the beneficial effect of a fresh whole blood transfusion?
Approximately 48 hours
217
What should be administered to prevent gastrointestinal adverse effects of glucocorticoids?
* H2 blockers (e.g., famotidine) * Proton pump inhibitors (e.g., omeprazole) * Sucralfate
218
What should be avoided in dogs with Evans syndrome due to the risk of exacerbating hemorrhage?
Heparin
219
What is the prognosis for dogs with ITP?
Good to guarded, with a short-term survival rate of 74% to 93%
220
What is the prognosis for dogs with megakaryocytic hypoplasia?
Poor prognosis
221
What is the prognosis for dogs with concurrent IMHA and ITP?
Poor, with reported mortality rates as high as 80%
222
What is the characteristic of primary feline immune-mediated thrombocytopenia?
Extremely rare disorder
223
What is recommended as an adjunctive immunosuppressant for cats that do not respond to glucocorticoids?
Chlorambucil
224
What is more common in cats leading to pseudothrombocytopenia?
Platelet clumping
225
What platelet count should be evaluated in asymptomatic thrombocytopenic cats?
Platelet count performed in citrate or heparin tubes
226
What is immune-mediated neutropenia (IMN)?
A rare condition in dogs and cats accounting for approximately 0.4% of neutropenia cases, characterized by the presence of serum antineutrophil IgG antibodies.
227
What are the clinical signs of immune-mediated neutropenia in dogs?
Common clinical signs include fever, lameness, anorexia, and lethargy.
228
What is the median age of dogs affected by immune-mediated neutropenia?
The median age is 5 years.
229
What percentage of dogs diagnosed with IMN have concurrent immune-mediated thrombocytopenia (ITP)?
Up to 25%.
230
How is a clinical diagnosis of IMN made?
By exclusion of other causes of neutropenia and detection of antineutrophil antibodies.
231
What is the initial treatment for immune-mediated neutropenia?
Glucocorticoids at an initial dose of 2-4 mg/kg/day of oral prednisone.
232
What are the types of immune-mediated polyarthritis?
Primary and secondary polyarthritis.
233
What is the hallmark of immune-mediated polyarthritis?
Nonseptic inflammation within the synovial membrane of two or more joints.
234
What diagnostic test is crucial for confirming immune-mediated polyarthritis?
Analysis of synovial fluid collected from affected joints.
235
What are common clinical signs of immune-mediated polyarthritis?
Joint pain, swelling, fever, anorexia, and lethargy.
236
What is the primary treatment for primary immune-mediated polyarthritis?
Immunosuppressive dosages of prednisone/prednisolone.
237
What are the common breeds predisposed to systemic lupus erythematosus (SLE)?
German Shepherd, Shetland Sheepdog, Collie, Beagle, and Poodle.
238
What is the most common clinical sign of SLE in dogs?
Fever (100%).
239
What type of hypersensitivity is primarily involved in SLE?
Type II and type III hypersensitivity.
240
What is the significance of a positive antinuclear antibody (ANA) titer in SLE?
It is a sensitive test to confirm the diagnosis of SLE.
241
What percentage of SLE patients show proteinuria from glomerulonephritis?
65%.
242
What is the recommended diagnostic approach for suspected SLE?
CBC, serum biochemical profile, urinalysis, and collection of synovial fluid.
243
What is a common complication in dogs with primary immune-mediated polyarthritis?
Relapses are common, and some dogs may require lifelong therapy.
244
Fill in the blank: Immune-mediated polyarthritis is primarily a type ______ hypersensitivity disorder.
III
245
True or False: Secondary immune-mediated polyarthritis typically resolves with appropriate treatment.
True
246
What are the common abnormalities detected on CBC in dogs with IMN?
Severe neutropenia, thrombocytopenia, mild anemia, hyperglobulinemia, increased alkaline phosphatase.
247
What is the role of C-reactive protein (CRP) in monitoring immune-mediated polyarthritis?
It is a nonspecific marker of inflammation and may be useful to monitor response to therapy.
248
What is the prognosis for idiopathic nonerosive polyarthritis treated with prednisone?
Good, with a mortality/euthanasia rate of less than 20%.
249
What is the key feature of the clinical course of SLE?
Relapsing and remitting course.
250
What viruses should be tested for in any cat with suspected SLE?
Feline leukemia virus, feline immunodeficiency virus, and feline infectious peritonitis ## Footnote These viruses are relevant because they can present symptoms similar to those of SLE.
251
What is the most commonly accepted test to confirm the diagnosis of SLE in dogs?
Measurement of serum ANA titer ## Footnote The sensitivity of this test ranges from 50% to 100%.
252
What factors contribute to the variability in diagnostic sensitivity of the ANA test?
Variation in diagnostic criteria and populations of dogs tested ## Footnote This variability can lead to different outcomes in test results.
253
What percentage of dogs with seroreactivity to certain pathogens may be ANA positive?
10% to 20% ## Footnote This includes dogs reacting to Bartonella vinsonii, E. canis, and Leishmania infantum.
254
What was the outcome of the study measuring ANA titer in dogs without major signs of SLE?
Only 1 of 47 dogs tested had immune-mediated disease and was seronegative for ANA ## Footnote The study emphasized the importance of patient selection for testing.
255
What is the LE test's clinical utility for diagnosing SLE?
Rarely used due to very low sensitivity ## Footnote Other antibody tests have not been extensively evaluated in dogs.
256
What is the initial treatment for SLE in dogs?
High doses of prednisone/prednisolone (1-2 mg/kg PO q12h) ## Footnote The dosage is tapered if disease remission is achieved.
257
What additional drugs may be necessary to maintain remission in SLE treatment?
Azathioprine, cyclosporine, mycophenolate ## Footnote These adjunctive immunosuppressive drugs are commonly added.
258
What is the prognosis for dogs diagnosed with SLE?
Guarded to poor ## Footnote Relapse is common, and long-term therapy is often required.
259
What is the most common cause of acquired glomerulonephritis (GN) in dogs?
Presence of immune complexes within the glomerular capillary walls ## Footnote This condition is more common in dogs than in cats.
260
What are the two ways immune complexes can form in the glomerulus?
* Circulating antigen-antibody complexes deposited in the glomerulus * In situ formation when antibodies react with glomerular antigens ## Footnote This differentiation is important for understanding the etiology of GN.
261
What pattern is observed on staining when soluble circulating immune complexes are deposited?
Granular pattern ## Footnote This can be seen on immunofluorescent or immunoperoxidase staining.
262
What is a potential cause of in situ deposition of immune complexes?
* Autoimmune disease with antibodies against the basement membrane * Localization of antigen in the glomerular capillary wall ## Footnote An example includes heartworm disease where Dirofilaria immitis antigens adhere to the glomerular capillary wall.
263
What are the consequences of immune complex deposition?
Severe proteinuria, systemic hypertension, renal failure, predisposition to thromboembolism ## Footnote Refer to Chapter 40 for more details on immune complex deposition consequences.
264
What is the hallmark of glomerulonephritis (GN)?
Proteinuria ## Footnote Proteinuria is readily detected on routine urinalysis.
265
What are common clinical signs of renal failure in animals?
* Anorexia * Weight loss * Vomiting * Polyuria * Polydipsia
266
What defines nephrotic syndrome?
Presence of proteinuria, hypoalbuminemia, hypercholesterolemia, and either peripheral edema or ascites
267
How is protein-losing nephropathy (PLN) diagnosed?
Documentation of persistent proteinuria not explained by lower urinary tract inflammation or blood contamination
268
What is the abnormal protein-to-creatinine ratio indicative of PLN?
Greater than 0.5 is abnormal; most dogs and cats with PLN have a ratio greater than 2.0
269
What diagnostic tests should be performed for PLN?
* CBC * Serum biochemical profile * Urinalysis and urine culture * Blood pressure * Radiographs of thorax and abdomen * Ultrasonography of kidneys
270
What is the recommended treatment for immune-mediated GN?
* Treat underlying disease * Decrease protein loss in urine * Decrease thromboembolism risk * Dietary therapy and supportive care
271
What medication is the most effective treatment for proteinuria?
Angiotensin-converting enzyme inhibitors (ACEIs) like enalapril
272
What is the role of anticoagulation in dogs with GN?
To decrease the likelihood of thromboembolism, especially in those with documented antithrombin deficiency
273
What is the first-line treatment for acquired Myasthenia Gravis (MG)?
Oral or injectable anticholinesterase inhibitors such as neostigmine or pyridostigmine
274
What is a common clinical presentation of Myasthenia Gravis?
Generalized weakness, either with or without concurrent megaesophagus
275
What is the primary autoimmune disorder associated with Myasthenia Gravis?
Antibodies against the nicotinic acetylcholine receptor (AChR)
276
What diagnostic test confirms Myasthenia Gravis?
Measurement of serum autoantibodies against AChR by immunoprecipitation radioimmunoassay
277
What are the clinical signs of focal Myasthenia Gravis?
Regurgitation due to megaesophagus, dysphagia, dysphonia, cranial nerve dysfunction
278
What are common breeds predisposed to Myasthenia Gravis?
* Akita * Various Terrier breeds * German Shorthaired Pointer * Abyssinian * Somali cats
279
What is the treatment for perianal fistula?
* Cyclosporine * Prednisone * Azathioprine * Tacrolimus (topical) * Supportive care
280
What is the most common breed affected by perianal fistula?
German Shepherds
281
What are the clinical signs of perianal fistula?
* Excessive grooming * Self-mutilation * Tenesmus * Hematochezia * Fecal incontinence
282
What histological features are seen in perianal fistula?
* Infiltration by lymphocytes and plasma cells * Presence of eosinophils and macrophages * Predominantly T cells with high concentrations of IL-2 and TNF-α
283
What is the prognosis for perianal fistula?
Guarded due to the chronic nature of the disease and common recurrence
284
What is masticatory myositis?
A focal myositis affecting the muscles of mastication characterized by unique muscle fiber type (type 2M)
285
What are common clinical signs of masticatory myositis?
* Inability to open the mouth (trismus) * Swelling and/or pain of masticatory muscles * Severe muscle atrophy
286
In which dogs is masticatory myositis most commonly found?
Young large-breed dogs, no specific breed predisposition except for juvenile-onset in Cavalier King Charles Spaniels
287
What breed is overrepresented in juvenile-onset masticatory myositis?
Cavalier King Charles Spaniels ## Footnote This syndrome has been specifically reported in this breed.
288
What are the clinical signs of masticatory myositis?
Inability to open the mouth (trismus), swelling and/or pain of the masticatory muscles, severe muscle atrophy, fever, depression, weight loss, dysphagia, dysphonia, and exophthalmos ## Footnote The acute phase may show muscle swelling and pain, while chronic phase shows severe muscle atrophy.
289
What is the primary method for diagnosing masticatory myositis?
Presence of antibodies against type 2M fibers ## Footnote This test is positive in greater than 80% of cases with high specificity.
290
What is the treatment for masticatory myositis?
Immunosuppressive doses of corticosteroids (prednisone 2-4 mg/kg PO q24h) ## Footnote Tapering the dose is necessary once clinical signs resolve.
291
What complications can arise from forcefully opening the jaws of a dog with masticatory myositis?
Fracture or luxation of the temporomandibular joint ## Footnote Force should never be used in this condition.
292
What is polymyositis characterized by?
Multifocal or diffuse infiltration of skeletal muscle by lymphocytes and negative serology for infectious disease ## Footnote It is primarily autoimmune but may be associated with malignancies.
293
Which breeds are most commonly affected by polymyositis?
Boxers, Newfoundlands, and Vizslas ## Footnote Polymyositis is uncommon in dogs and rare in cats.
294
What are common clinical signs of polymyositis?
Generalized weakness, stiff gait, cervical ventriflexion, pain on palpation of muscles, dysphagia, generalized muscle atrophy, dysphonia, tongue atrophy, fever, and megaesophagus ## Footnote Megaesophagus is reported in 15% of cases.
295
How is polymyositis diagnosed?
Characteristic clinical signs, elevated creatine kinase level, electrophysiologic testing abnormalities, serology for infectious causes, and muscle biopsy ## Footnote It is crucial to rule out infectious causes in these cases.
296
What is dermatomyositis?
An uncommon immune-mediated disorder affecting the skin, skeletal muscle, and vasculature ## Footnote Common in Collies and Shetland Sheepdogs with an autosomal-dominant inheritance pattern.
297
At what age do lesions typically develop in dermatomyositis?
Between 2 and 4 months of age ## Footnote Signs of myositis develop later.
298
What is the treatment protocol for dermatomyositis?
Symptomatic care of cutaneous lesions and immunosuppression ## Footnote Prolonged corticosteroid therapy is necessary and relapses are common.
299
What is the prognosis for dogs with mild versus severe dermatomyositis?
Good for mild cases, poor for severely affected dogs ## Footnote Severity of the condition plays a significant role in prognosis.
Nelson and Couto
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