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Also known as: '''''SLE — Multi-Systemic Immune Mediated Disease
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Also known as: '''''SLE'''''
    
==Introduction==
 
==Introduction==
Systemic Lupus Erythematous is an immune-mediated disease which can affect many different organ systems. The immune system is directed against various tissues of the body and immune complexes cause a [[Type III Hypersensitivity|type III hypersensitivity reaction]]. The condition is documented in cats and dogs but the etiology is not known. The disease has been reported in colonies of dogs suggesting that there may be a genetic or infectious component to the cause.
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Systemic Lupus Erythematous is an immune-mediated disease which can affect '''many different organ systems'''. It is an primary autoimmune disease in which the body loses 'self-tolerance' towards autoantigens and mounts an inappropriate attack on various target tissues of the body. The pathology can be attributed to true autoantibody binding, '''immune complex deposition''' causing a [[Type III Hypersensitivity|type III hypersensitivity reaction]], or cell-mediated autoimmunity.  
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The most well-studied autoantibodies formed are the '''Anti-Nuclear Antibodies''' (ANA) which are found in up to 100% of cases reported and are important in the diagnosis of the disease. These target a number of nuclear components, including double-stranded DNA, histones and extractable nuclear antigens.
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The '''aetiology''' of the disease is multifactorial, involving genetics, immunological disorder, viral infection and hormonal and ultraviolet light modulation.
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The condition is uncommon in dogs and rare in cats and horses.
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==Clinical Signs==
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Clinical signs are varied and changeable. SLE is able to mimic numerous diseases and is sometimes called ''''the great imitator''''.
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<u>Dogs</u>: there is no age predilection, but male are more commonly affected.  
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The most common manifestations are: '''fever''' (constant or cyclic), '''polyarthritis''' (non-erosive, non-deforming), proteinuria and '''skin disease'''.
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Skin changes include: periorbital alopecia, seborrhea, oral ulceration, [[Discoid Lupus Erythematosus]], mucocutaneous ulcerations, footpad ulceration, panniculitis and urticaria. Skin changes can be multifocal or generalised, and commonly involve skin poorly covered by hair. Lesions may be exacerbated by exposure to light.
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Other common manifestations include: '''anaemia, leucopaenia, peripheral lymphadenopathy, splenomegaly'''.
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Other reported syndromes include: pericarditis, thrombocytompaenia, polymyositis, myocarditis, pneumonitis, pleuritis, neutrologic disorders (seizures, meningitis, psychosis) and lymphoedema.
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<u>Cats</u>: no age predilection, but Siamese, Himalayan and Persian breeds may be predisposed.
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Cat report syndromes such as: haematological abnormalities, neurological abnormalities, fever, lymphadenopathy, polyarthritis, myopathy, oral ulceration, conjunctivitis, '''renal failure''' and subclinical pulmonary disease.
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Only 20% of cats will have skin lesions such as seborrhea, erythema, alopecia and scarring on the face, pinnae and paws.
    
==Diagnosis==
 
==Diagnosis==
===Clinical Signs===
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Diagnosis of SLE is made on a combination of clinical findings, haemotologic, serum biochemistry and immunological testing results. Diagnosis can be '''challenging''' as the condition can mimic a number of other diseases. Ruling out differential diagnoses will help in securing a definitive diagnosis.  
Clinical signs depend on the tissues and organ systems affected by the condition. A combination of the following signs may be seen:
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* Immune-mediated haemolytic anaemia
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* Immune-mediated thrombocytopenia
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* Polyarthritis
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* Glomerulonephritis
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* Vasculitis
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* Dermatitis
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* Seizures
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The most widely accepted diagnostic criteria for the disease is that an animal should have at least '''2 separate clinically and serologically defined manifestations of autoimmunity in addition to a high serum titre of ANA'''.
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Diagnosis of SLE is made on a combination of clinical findings, haemotologic, serum biochemistry and immunological testing results. Diagnosis can be challenging as the condition can mimic a number of other diseases. Ruling out differential diagnoses will help in securing a definitive diagnosis.
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'''Haematology and biochemistry''' may reveal: anaemia with or without a positive direct Coombs' test result, thrombocytopaenia, leucopaenia or leucocytosis, proteinuria and hypergammaglobulinaemia.
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The '''ANA test''' is considered the most sensitive serological test for SLE. However it is not the most specific of tests, and can be positive in up to 20% of dogs with infectious diseases, particularly leishmaniasis. It is important to record the titre and compare it with normal values for the same laboratory.
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The Lupus Erythematosus '''(LE) test''' is not as valuable, varies from day to day, and lacks specificity and sensitivity.  
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'''Pathology''' findings in the skin include: lymphohistiocytic interface dermatitis, thickened basement membrane, vasculitis, subepidermal vesicles, basal cell degeneration
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===Laboratory Tests===
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A positive antinuclear antibody (ANA) test is supportive of a diagnosis of SLE.
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==Treatment==
 
==Treatment==
Treatment is with immunosuppressive drugs. Corticosteroids are the most widely used immunosuppresive drugs, prednisolone or dexamethasone is used alone or in combination with azathioprine or cyclophosphamide in more severe cases. Typically the dose can be tapered once the condition is under control.   
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Treatment is with '''immunosuppressive drugs'''.  
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The initial agent of choice is large doses of systemic glucocorticoids such as '''prednisolone'''.
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Other drugs may be useful in combination if the response is not satisfactory, and '''azathioprine or cyclophosphamide''' can be used. Typically the dose can be tapered once the condition is under control.   
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'''Splenectomy''' may be necessary in animals with severe anaemia and thrombocytopaenia. '''Vinctristine''' can be useful when thrombocytopaenia is severe.
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Animals with SLE are prone to infections and therefore any infections must be identified and dealt with effectively and quickly.
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Specific supportive care may be necessary for animals with renal disease, such as dietary manipulation.
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'''ANA titres''' can be monitored throughout treatment as levels usually fall with clinical improvement, thought the antibody may persist at lower titres during clinical remission.
    
==Prognosis==
 
==Prognosis==
Prognosis is good with appropriate treatment.
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Prognosis is '''unpredictable''' and depends on the organs involved.
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The earlier the diagnosis is made, the better the prognosis.
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In general, dogs with muscle, joint and skin disease respond more reliably to medical treatment and remain in remission for longer than animals with severe haemolytic anaemia, thrombocytopaenia or glomerulonephritis.
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Over 40% of dogs with SLE are '''dead within 1 year''' after the diagnosis is made, either from disease or from euthanasia.
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{{Learning
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|flashcards = [[Veterinary Dentistry Q&A 15]]
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}}
    
==Literature Search==
 
==Literature Search==
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==References==
 
==References==
* Blood, D.C. and Studdert, V. P. (1999) '''Saunders Comprehensive Veterinary Dictionary (2nd Edition)''' ''Elsevier Science''
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Blood, D.C. and Studdert, V. P. (1999) '''Saunders Comprehensive Veterinary Dictionary (2nd Edition)''' ''Elsevier Science''
* Merck & Co (2008) '''The Merck Veterinary Manual (Eighth Edition)''' ''Merial''
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* Nelson, R.W. and Couto, C.G. (2009) '''Small Animal Internal Medicine (Fourth Edition)''' ''Mosby Elsevier''
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==From Pathology==
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*'''Systemic (SLE)'''
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Merck & Co (2008) '''The Merck Veterinary Manual (Eighth Edition)''' ''Merial''
**Multiple organs involved
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**Cats, dogs, horses
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**Immune dysregulation:
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***Damaged T-cell suppressor function, either primary deficiency or antibody mediated
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***Cytokine dysregulation
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***Resulting B-cell hyperactivity -> antibodies to self antigens -> antigen-antibody complexes deposited in various tissues -> Type III hypersensitivity
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**Lesions localised or generalised
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**Erythema, alopecia, depigmentation, crusting and scaling, ulceration
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**Microscopically: lymphohistiocytic interface dermatitis, thickened basement membrane, vasculitis, subepidermal vesicles, basal cell degeneration
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Nelson, R.W. and Couto, C.G. (2009) '''Small Animal Internal Medicine (Fourth Edition)''' ''Mosby Elsevier''
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*Also see [[Discoid Lupus Erythematosus]]
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Muller, G. (2001) '''Small animal dermatology''' ''Elsevier Health Sciences''
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Pasquini, C. (1999) '''Tschauner's Guide to Small Animal Clinics''' ''Sudz Publishing''
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[[Category:To Do - Helen]]
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[[Category:To Do - Review]]
    
[[Category:Integumentary System - Autoimmune Reactions]]
 
[[Category:Integumentary System - Autoimmune Reactions]]
 
[[Category:Antibody Mediated Autoimmune Diseases]]
 
[[Category:Antibody Mediated Autoimmune Diseases]]
 
[[Category:Immunological Diseases - Cat]][[Category:Immunological Diseases - Dog]]
 
[[Category:Immunological Diseases - Cat]][[Category:Immunological Diseases - Dog]]
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