Immune mediated diseases Flashcards
What are the different types of immune mediated disease?
-
Hypersensitivity (allergic) diseases
◦ dermatological disorders; dietary intolerances; asthma
◦ Hypersensitivity reactions (usually T1, sometimes T4) -
Autoimmune Diseases
◦ Failure of self-tolerance….. Quite rare as self-tolerance is usually good!
◦ Influenced by: age; hormones; genetics; environment (eg exposure to microbes, drugs or vaccination)….. OR the immune system is affected by something else, typically neoplasia or infection. -
Immune system neoplasia
◦ Lymphoid cell neoplasia
‣ Common- lymphoma (FeLV +/-), lymphoid leukaemia; cutaneous histiocytoma
‣ More rare (precursors affected) – Multiple myeloma, plasmacytoma, histiocytic sarcoma -
Immunodeficiency diseases/disorders
◦ Congenital – Primary immunodeficiency – diseases where the immune system does not function normally
‣ white cells aren’t there or aren’t functional
‣ not the one we see most
◦ Acquired – failure of passive transfer (colostrum); chronic infections eg FIV; inflammatory or neoplastic diseases; drugs; malnutrition; toxins, stress which stop a normal immune response.
‣ steroid induced immune deficiency - after high dose of steroids
How can we categorise the causes of immune mediated disease?
Primary (idiopathic)
* Caused by underlying dysfunction or imbalance in the immune system
◦ inappropriate response to self antigen
* Might need to exclude causes of secondary disease before having the confidence to treat
Secondary
* Triggers include
◦ infection
◦ inflammatory disease
◦ Drugs – eg TMPS
◦ neoplasia
◦ (vaccination?…conflicting evidence)
◦ environment
What is this typical for?
Babesia - alien eyes
red blood cell looks weird and so immune system will target them
What is immunodeficiency? What are the 2 types?
a functional problem with the immune system
Primary immunodeficiency – genetic; rare
* May affect eg neutrophils, lymphocytes, immunoglobulins
* repeated infections in a young animal post weaning or after loss of maternal antibody
* pure bred puppy or several puppies from a litter experiencing problems
Secondary immunodeficiency – many causes; more common
* Immunosenescence - immune system gets older with animal
* Medical immunosuppression
* Specific infections eg FIV, parvovirus
* Chronic disease
Is immune mediated disease relevant clinically?
AI diseases are uncommon BUT can be serious +/or life threatening
* usually have no gold standard diagnostic test
* need to exclude other diseases
* diagnostic tests can have false +ve and false –ve results
* diagnosis can be challenging
* mimic other diseases and/or can be triggered by other diseases
◦ identify and treat the underlying cause if possible
* require prolonged treatment with drugs that may have adverse effects
* may just need treatment for the consequences: eg hypoadrenocorticism, hypothyroidism
What are the major immune-mediated diseases in dogs and cats?
Immune mediated diseases are less common in cats than in dogs
-
Haemolymphatic
◦ IMHA
◦ IMTP
◦ Immune mediated neutropenia (rare!) -
Endocrine
◦ Hypothyroidism
◦ Hypoadrenocorticism -
Cutaneous
◦ Canine dermatomyositis
◦ Discoid lupus erythematosus (DLE)
◦ Pemphigus-pemphigoid complex -
Musculoskeletal/neuromuscular
◦ Polyarthritis (erosive and non-erosive)
◦ Myasthenia gravis (neuromuscular)
‣ focal vs. generalised
◦ Polymyositis/polyneuritis -
CNS
◦ MUO
◦ Granulomatous meningioencephalitis (GME) -
GI
◦ Inflammatory bowel disease/chronic enteropathy (IBD/CE)
◦ Pancreatitis in Cocker Spaniels
‣ +/- other breeds -
Renal
◦ Glom erulonephropathies (many) -
Multi-systemic involvement
◦ Systemic lupus erythematosus (SLE)
◦ many are poorly categorised but may see collections of clinical signs
‣ polyarthrtitis and meningitis
‣ pancreatitis and dry eye in cocker spaniels
Which of the following factors is most relevant in predisposing a dog to a primary immunodeficiency disorder?
* Genetics
* Environmental factors such as stress
* An infectious trigger eg canine parvovirus
* The use of immunosuppressive doses of glucocorticoids
* Increasing age
Genetics
What are the 2 types of IMHA?
Primary IMHA
* No known causative trigger
* Associated with an inherited predisposition in dogs
◦ most commonly cocker spaniels, springer spaniels, and poodles.
Secondary IMHA
* The trigger or cause is an underlying condition, either recently or historically
* Infection – eg Mycoplasma haemofelis; Babesia canis, FIP, FeLV, chronic bacterial
* Neoplasia – eg splenic haemangiosarcoma
* Drugs, toxins, vaccination – eg TMPS, methimazole
* Envenomation – snake bite, bee sting
Approx 65-70% of cases in dogs have primary (idiopathic) IMHA cf 30-35% with secondary IMHA
What happens in IMHA?
Intra vascular haemolysis
* direct lysis of RBCs due to antibody binding and complement activation
◦ implies a high concentration of antibody-> more severe disease?
* less common than extra vascular haemolysis but more acute
* release of free haemoglobin in to plasma
◦ red/pink plasma +/- red/pink urine
Extra vascular haemolysis
* antibody binding to RBCs stimulates phagocytosis by mononuclear cells in the liver and spleen
* spherocytes are formed if partial phagocytosis occurs
◦ useful marker for IMHA in a peripheral blood smear
* cats: phagocytosis can occur with
◦ intracellular rbc parasites
◦ Heinz bodies (oxidative damage)
* Haemoglobin metabolised by liver
◦ Too much -> jaundice
* essentially the macrophages in liver and spleen “recognise” the abnormal red cells (antibody or complement binding, abnormal or damaged cells) and remove them from circulation. Normally only ageing red cells are removed by liver and spleen. Premature removal in this way leads to anaemia.
What is IMHA triggered by in cats?
- Is often secondary and can be triggered by:
◦ FIP
◦ Mycoplasma haemofelis
◦ FeLV
◦ Chronic bacterial infections
What do we see clinically in IMHA?
Hepatomegaly - working really heard to metabolise RBCs
Pale mucous membranes
Jaundice
What do you expect to see on haematology in IMHA?
-
Confirm the presence of anaemia:
◦ PCV low, total solids usually normal- consistent with haemolysis
‣ what colour is the plasma?
◦ anaemia is usually moderate to marked (PCV/HCT <20%) -
Is the anaemia regenerative or non regenerative?
◦ degree of regenerative response depends on the magnitude of the anaemia
‣ what are the features of a regenerative anaemia?
◦ could the anaemia be pre-regenerative if per-acute presentation?
‣ how long does it take for the bone marrow to mount a regenerative response? -
What are other cell lines doing?
◦ neutrophilia is common with a shift towards immature cell lines
‣ bands, metamyelocytes
◦ are there enough platelets or could there be combined IMHA and IMTP?
‣ mild thrombocytopenia is not uncommon and not significant
What do you see on the blood smear in IMHA?
◦ are there any spherocytes? (hard to see in cats)
◦ is there evidence of an inflammatory leucogram?
◦ can you confirm an automated platelet count?
◦ are there any abnormal cells suggesting myeloproliferative disease?
What tests can you do to diagnose IMHA?
- auto-agglutination
- Coombe’s test
What do you expect to see on biochem and urinalysis in IMHA?
Biochemistry
* What colour is the serum/plasma
◦ orange/yellow = bilirubinaemia
◦ red = haemoglobinaemia
* What might you expect to see?
◦ raised liver enzymes indicating hepatocellular damage (ALT) and resulting cholestasis (ALP) are common
‣ associated with anaemia and hypoxic liver damage
◦ high bilirubin which with a low PCV/anaemia is consistent with pre hepatic jaundice
* Is there any evidence of an underlying disease that could be a trigger for IMHA?
Urinalysis
* Usually consistent with bilirubinuria or haemoglobinuria
* Consider sediment analysis and culture in case UTI is a trigger for IMHA
How can you treat IMHA?
◦ Treat the underlying trigger/ disease where possible
‣ Antibiotics?
◦ Immunosuppression
‣ Glucocorticoids
‣ Azathioprine
‣ Mycophenolate Mofetil
‣ Cyclosporin
‣ Leflunomide
During the initial treatment of IMHA, thromboprophylactic therapy is recommended:
* unfractionated heparin
* injectable low molecular weight heparins such as enoxaparin
* rivaroxaban
* Oral antiplatelet agents such as clopidogrel
* low-dose aspirin
Which of the following tests or findings is the most sensitive for a diagnosis of immune-mediated haemolytic anaemia (IMHA)?
* Saline agglutination test
* Low packed cell volume (PCT)
* Coombe’s test/ Direct antiglobulin test (DAT)
* Spherocytosis
* Anaemia with hepatomegaly
Coombe’s test/ Direct antiglobulin test (DAT)
What are the 2 types of IMTP?
Primary IMTP = autoimmune disorder with production of antibodies directed against normal platelet antigens. This is usually IgG directed against surface glycoproteins.
-> middle-aged female dogs, cocker spaniels, Old English sheepdogs, GSDs, and poodles.
Secondary IMTP = antibodies target nonself antigens adsorbed onto the surface of platelets or when immune complexes become bound to platelet surfaces.
Associated with :
* infection,
* drug therapy,
* neoplasia,
* poly- immune syndromes
* Vaccination as a cause of secondary IMT is possible.
What clinical presentation is IMTP assocated with?
- Often subclinical
- Will present either of signs of concurrent anaemia or with bleeding once things are more severe.
- Bleeding with thrombocytopaenia is rare but can occur spontaneously when PLT < 50,000/L
◦ petechiae, ecchymoses, haematomas
◦ epistaxis
◦ gingival bleeding
◦ melaena/haematochezia from bleeding into the GIT
◦ haematuria from bleeding into the urinary tract
◦ retinal haemorrhage, hyphaema, anterior uveitis
◦ Intracavitary bleeding is very rare.
What lab findings would you get with IMTP?
- Low platelet count – automated or manual count. NB – check for clumping.
- In primary IMTP – biochemistry profiles and coagulation tests are often normal
- Haematology – check for concurrent anaemia and/or concurrent cell line reductions which could indicate bone marrow disease
Infectious Disease Testing
* Ehrlichiosis, Rocky Mountain spotted fever, anaplasmosis, histoplasmosis, leishmaniasis, and distemper have been associated with secondary IMT
How would you treat IMTP?
Acute treatment
* Transfusion – often not needed though bleeding risk increases <20,000/μL,.
◦ Platelet transfusions available in USA, BUT variable response - Blood or platelet transfusions do not significantly raise the platelet count,
* Vincristine immunosuppressant activity, may induce thrombocytosis in 7 days.
Long-term treatment options
* Immunosuppression
◦ Prednisolone initially
◦ Azathioprine (can take more than 4 weeks to effect)
‣ Cyclosporine
‣ Mycophenolate mofetil - variable response. Consider use in refractory cases.
‣ Leflunomide has shown efficacy in anecdotal reports, but studies are limited.
What would be the primary indication for blood product transfusion in an anaemic cat, PCV 22% (25-45%) following a traumatic road traffic accident?
* PCV not increasing after 24 hours
* PCV below 20% at any point
* Gums getting more pale
* Cardiovascular deterioration
* Development of hypothermia
Cardiovascular deterioration
When should you transfuse?
- There is no magic “PCV”…. a decision to transfuse is based on clinical signs:
◦ tachycardia
◦ poor pulse quality
◦ weakness
◦ tachypnoea
◦ collapse - Rapid fall in PCV:
◦ <20% dogs
◦ <10-15% cats
