Difference between revisions of "Infectious Canine Hepatitis"

Revision as of 11:53, 4 August 2010

Also known as:

Rubarth's Disease
Canine adenovirus infection

Description

Infectious Canine Hepatitis (ICH) is a highly contagious disease of dogs caused by Canine Adenovirus 1 (CAV1). This virus is closely related to Canine Adenovirus 2, which causes respiratory disease.

Canine Adenovirus 1 invades via the oronasal route following excretion in the urine and faeces. Urinary excretion can persist for up to nine months after an active infection, and the virus may also be spread by contaminated fomites. Once established, CAV1 replicates in the cells of the oropharynx before a viraemia causes dissemination to other tissues. A trophism exists for hepatic parenchyma and vascular endothelium: the target organs of CAV1 are therefore the liver, kidney, vascular endothelium and eye.

In the liver, the clinical outcome of CAV1 infection depends on the level of pre-existing immunity. Animals with high antibody titres usually mount an effective neutralising antibody response by day seven post-infection which clears the virus. Outcome is variable when a partial antibody response is mounted four to five days post-infection: both chronic active hepatitis (and ultimately hepatic fibrosis) and latent hepatic infection are possible. Low antibody titres, such as in unvaccinated dogs, fail to prevent infection and pathology and lead to potentially fatal hepatic necrosis. This necrosis is initially widespread and centrilobular, but may progress to become panlobular. In the kidney, virus localisation or deposition of circulating immune complexes causes glomerular damage and thus proteinuria. Immune complexes may also be deposited in the cornea and uveal tract, damaging the eye. In addition to glomerular localisation, CAV1 persists in the renal tubular epithelium which accounts for the extended period of urinary excretion. Virus replication in the vascular endothelium leads to vasculitis and bleeding diatheses, and direct cytoxic damage to the eye is also possible.

Signalment

Young, unvaccinated dogs are most often affected.

Diagnosis

Clinical Signs

Signs may be peracute or acute in onset. In acute cases, the key clinical findings are vomiting, abdominal pain, anorexia, diarrhoea and pyrexia. Some cases may also show signs of a bleeding disorder. However, there are many different features that clinical examination could possibly reveal. These might include:

Abdominal distension and/or pain
Hepatomegaly
Jaundice
Petechial or ecchymotic haemorrhages
Epistaxis
Bleeding from venipuncture sites
Pneumonia
Lymphadenopathy
Pharyngitis or tonsilar enlargement
CNS signs such as depression, disorientation and seizures.

Clinical signs generally persist for five to seven days before the animal's condition improves. During the recovery phase, 20% of cases develop corneal oedema and anterior uveitis ("blue eye"). In peracute cases, death rapidly follows the onset of clinical signs.

Laboratory Tests

Routine haematology and blood biochemistry may show several changes. Leucocytes are initally depleted due to neutropenia and lymphopenia, but recovering animals display leucocytosis and neutrophilia. The liver enzymes ALT, AST and SAP tend to be raised, and liver function is impaired. This is demonstrated by elevations in bile acids, ammonia and bilirubin. Clotting abnormalities such as thrombocytopaenia and prolonged PT and APTT may also be noted. However, although indicative of heptatic disease, these tests are non-specific for infectious canine hepatitis.

Other laboratory tests may be used in the confirmation of CAV1 infection. Although virus isolation (on tissues or secretions) and immunofluorescence (on infected tissues) are both possible, serology is the most useful adjunctive test. CAV1 antibodies typically increase to levels greater than those post-vaccination during active infection, and so a rising antibody titre can confirm a diagnosis if infectious canine hepatitis.

Radiography

Hepatomegaly may be seen on radiography.

Biopsy

Impression smears made of the liver may be stained to show nuclear inclusion bodies, and centrilobular necrosis is typically seen on liver biopsy. For more information, please see the details on histopathology below.

Endoscopy

Pathology

Gross

The liver is enlarged and friable on post-mortem examination. Extensive centrilobular necrosis leads to a pale, mottled appearance, but widespread haemorrhage is also apparent. These haemorrhages are located particularly on the serosal surface. Ascites results from this hepatitis, and fibrinous or fibrino-haemorrhagic adhesions can sometimes be seen between the lobes of the liver.

Other organs may also show changes. For example, the wall of the gall bladder may be oedematous, and lymph nodes can be enlarged, reddened and haemorrhagic. Chronic interstitial nephritis may feature.

Histological

Histopathology reveals centrilobular necrosis. Haematoxylin and eosin staining reveals basophilic intranuclear inclusion bodies in hepatocytes and macrophages. It is possible to use immunofluorescence to stain for viral antigen in vascular endothelium.

Treatment

Control

In an outbreak

Isolate infected dogs
Disinfect premises

To prevent

Vaccination: tissue culture adaptation that may be live or inactivated
Cross protection with CAV2
Live vaccines are known to cause keratitis in Afghans, Red Setters and Saluki

Prognosis

References

@@ Line 1: / Line 1: @@
-{{OpenPagesTop}}
+{{unfinished}}
-Also known as: '''''Rubarth's Disease — Canine adenovirus infection — ICH'''''
-==Introduction==
+{|cellpadding="10" cellspacing="0" border="1"
-Infectious Canine Hepatitis (ICH) is a highly contagious disease of dogs caused by [[Canine Adenovirus 1]] (CAV-1). This virus is closely related to [[Canine Adenovirus 2]], which causes respiratory disease.
+|Also known as:
+|Rubarth's Disease <BR> Canine adenovirus infection
+|}
-Canine Adenovirus 1 invades via the oronasal route following excretion in the urine and faeces and spread via fomites. Once established, CAV-1 replicates in the cells of the oropharynx before a viraemia causes dissemination to other tissues 4-8 days later. A trophism exists for hepatic parenchyma and vascular endothelium. In the liver, CAV-1 replicates in Kupffer cells and damages adjacent hepatocytes when released. Other parenchymal organs, namely the kidney, and the eye may also be affected in infectious canine hepatitis. When an adequate antibody response is mounted, organs may be cleared of virus within 10-14 days, but urinary excretion can persist for up to nine months after an active infection.
-In the liver, the clinical outcome of CAV-1 infection depends on the level of pre-existing immunity. Animals with high antibody titres usually mount an effective neutralising antibody response by day seven post-infection which clears the virus. Outcome is variable when a partial antibody response is mounted four to five days post-infection: both chronic active hepatitis (and ultimately hepatic fibrosis) and latent hepatic infection are possible. Low antibody titres, such as in unvaccinated dogs, fail to prevent infection and pathology and lead to potentially fatal hepatic necrosis. This necrosis is initially widespread and centrilobular, but may progress to become panlobular. In the kidney, virus localisation or deposition of circulating immune complexes causes glomerular damage and thus proteinuria. Immune complexes may also be deposited in the cornea and uveal tract, damaging the eye. In addition to glomerular localisation, CAV-1 persists in the renal tubular epithelium which accounts for the extended period of urinary excretion. Virus replication in the vascular endothelium leads to vasculitis and bleeding diatheses, and direct cytoxic damage to the eye is also possible.
+==Description==
+Infectious Canine Hepatitis (ICH) is a highly contagious disease of dogs caused by [[Canine Adenovirus 1]] (CAV1). This virus is closely related to Canine Adenovirus 2, which causes respiratory disease.
+Canine Adenovirus 1 invades via the oronasal route following excretion in the urine and faeces. Urinary excretion can persist for up to nine months after an active infection, and the virus may also be spread by contaminated fomites. Once established, CAV1 replicates in the cells of the oropharynx before a viraemia causes dissemination to other tissues. A trophism exists for hepatic parenchyma and vascular endothelium: the target organs of CAV1 are therefore the liver, kidney, vascular endothelium and eye.
+In the liver, the clinical outcome of CAV1 infection depends on the level of pre-existing immunity. Animals with high antibody titres usually mount an effective neutralising antibody response by day seven post-infection which clears the virus. Outcome is variable when a partial antibody response is mounted four to five days post-infection: both chronic active hepatitis (and ultimately hepatic fibrosis) and latent hepatic infection are possible. Low antibody titres, such as in unvaccinated dogs, fail to prevent infection and pathology and lead to potentially fatal hepatic necrosis. This necrosis is initially widespread and centrilobular, but may progress to become panlobular. In the kidney, virus localisation or deposition of circulating immune complexes causes glomerular damage and thus proteinuria. Immune complexes may also be deposited in the cornea and uveal tract, damaging the eye. In addition to glomerular localisation, CAV1 persists in the renal tubular epithelium which accounts for the extended period of urinary excretion. Virus replication in the vascular endothelium leads to vasculitis and bleeding diatheses, and direct cytoxic damage to the eye is also possible.
 ==Signalment==
+Young, unvaccinated dogs are most often affected.
+==Diagnosis==
-Infectious canine hepatitis affects unvaccinated dogs, particularly those of less than one year of age. There are no breed or sex predispositions.
-==Diagnosis==
 ===Clinical Signs===
-Signs may be peracute or acute in onset. Peracute cases are pyrexic and show CNS signs, vascular collapse and [[Disseminated Intravascular Coagulation|disseminated intravascular coagulation]], and die within hours. In acute cases, the key clinical findings tend to be pyrexia, vomiting, diarrhoea, abdominal pain and anorexia, and some cases also show signs of a bleeding disorder. However, there are many different features that clinical examination could possibly reveal, and these could include:
+Signs may be peracute or acute in onset. In acute cases, the key clinical findings are vomiting, abdominal pain, anorexia, diarrhoea and pyrexia. Some cases may also show signs of a bleeding disorder. However, there are many different features that clinical examination could possibly reveal. These might include:
 * Abdominal distension and/or pain
 * Hepatomegaly
-* [[Icterus|Jaundice]]
+* Jaundice
 * Petechial or ecchymotic haemorrhages
 * Epistaxis
@@ Line 28: / Line 41: @@
 * Pharyngitis or tonsilar enlargement
 * CNS signs such as depression, disorientation and seizures.
-Clinical signs generally persist for five to seven days before the animal's condition improves.
-In the late stage of disease, 20% of cases develop corneal oedema and anterior uveitis ("blue eye") 4-6 days post-infection. In most cases, these ocular signs resolve within 21 days but some may progress to corneal ulceration or glaucoma.
+Clinical signs generally persist for five to seven days before the animal's condition improves. During the recovery phase, 20% of cases develop corneal oedema and anterior uveitis ("blue eye"). In peracute cases, death rapidly follows the onset of clinical signs.
 ===Laboratory Tests===
-Routine haematology and blood biochemistry may show several changes. Leucocytes are initally depleted due to neutropenia and lymphopenia, but recovering animals display leucocytosis and neutrophilia. The liver enzymes ALT, AST and ASP tend to be raised, and liver function is impaired. This is demonstrated by elevations in [[bile acids]], [[ammonia]] and [[bilirubin]]. Clotting abnormalities such as [[Platelet Abnormalities|thrombocytopaenia]] and prolonged PT and APTT may also be noted. However, although indicative of hepatic disease, these tests are non-specific for infectious canine hepatitis.
+Routine haematology and blood biochemistry may show several changes. Leucocytes are initally depleted due to neutropenia and lymphopenia, but recovering animals display leucocytosis and neutrophilia. The liver enzymes ALT, AST and SAP tend to be raised, and liver function is impaired. This is demonstrated by elevations in bile acids, ammonia and bilirubin. Clotting abnormalities such as thrombocytopaenia and prolonged PT and APTT may also be noted. However, although indicative of heptatic disease, these tests are non-specific for infectious canine hepatitis.
-Other laboratory tests may be used in the confirmation of CAV-1 infection. Although virus isolation (on tissues or secretions) and immunofluorescence (on infected tissues) are both possible, serology is the most useful adjunctive test. CAV-1 antibodies typically increase to levels greater than those post-vaccination during active infection, and so a rising antibody titre can confirm a diagnosis of infectious canine hepatitis.
+Other laboratory tests may be used in the confirmation of CAV1 infection. Although virus isolation (on tissues or secretions) and immunofluorescence (on infected tissues) are both possible, serology is the most useful adjunctive test. CAV1 antibodies typically increase to levels greater than those post-vaccination during active infection, and so a rising antibody titre can confirm a diagnosis if infectious canine hepatitis.
+===Radiography===
+Hepatomegaly may be seen on radiography.
-===Diagnostic Imaging===
-Abdominal radiography may show the liver to be large or normally sized, and detail may be lost due to the presence of an [[:Category:Effusions|effusion]]. Ultrasonography may show hepatomegaly, multifocal to diffuse hypoechoic areas within the parenchyma, and effusion.
 ===Biopsy===
-Impression smears made of the liver may be stained with haemotoxylin and eosin to show intranuclear inclusion bodies in hepatocytes and macrophages. These are also seen on histopathology of liver biopsies, in addition to centrilobular necrosis.
+Impression smears made of the liver may be stained to show nuclear inclusion bodies, and centrilobular necrosis is typically seen on liver biopsy. For more information, please see the details on histopathology below.
+===Endoscopy===
 ===Pathology===
+====Gross====
+The liver is enlarged and friable on post-mortem examination. Extensive centrilobular necrosis leads to a pale, mottled appearance, but widespread haemorrhage is also apparent. These haemorrhages are located particularly on the serosal surface. Ascites results from this hepatitis, and fibrinous or fibrino-haemorrhagic adhesions can sometimes be seen between the lobes of the liver.
-The liver is enlarged and friable on post-mortem examination. Extensive centrilobular necrosis leads to a pale, mottled appearance, but widespread haemorrhage is also apparent. These haemorrhages are particularly obvious on the serosal surface. This hepatitis leads to ascites, and fibrinous or fibrino-haemorrhagic adhesions can sometimes be seen between the lobes of the liver. Other organs may also show changes. For example, the wall of the gall bladder may be oedematous, and lymph nodes can be enlarged, reddened and haemorrhagic. In chronic cases, the liver may be small, fibrotic or cirrhotic.
+Other organs may also show changes. For example, the wall of the gall bladder may be oedematous, and lymph nodes can be enlarged, reddened and haemorrhagic. Chronic interstitial nephritis may feature.
-Histopathology reveals centrilobular necrosis. Haematoxylin and eosin staining reveals basophilic intranuclear inclusion bodies in hepatocytes and macrophages. It is possible to use immunofluorescence to stain for viral antigen in vascular endothelium.
+====Histological====
+Histopathology reveals centrilobular necrosis. Haematoxylin and eosin staining reveals basophilic intranuclear inclusion bodies in hepatocytes and macrophages.
+It is possible to use immunofluorescence to stain for viral antigen in vascular endothelium.
 ==Treatment==
+===Control===
-Treatment for infectious canine hepatitis is supportive and symptomatic. Fluid therapy is essential, but care must be taken to avoid overhydration since vascular permeability may be increased. It may be necessary to monitor and supplement magnesium and potassium since depletion of electrolytes can compound [[Hepatic Encephalopathy|hepatic encephalopathy]]. Dextrose can also be added to fluids to avoid neuroglycopenia. Blood or plasma can be administered in the event of clotting disorders and in conjunction with heparin in disseminated intravascular coagulation. Nutritional support is important; frequent small meals containing adequate but not excessive protein should be given. Hepatic encephalopathy can be treated with [[lactulose]] and antibiotics such as neomycin or ampicillin, and prohpylactic antimicrobials also protect against bacteremia of intestinal microbes in hepatic failure. S-adenosyl methionine can be provided as a glutathione precursor, and vitamin E as an antioxidant, to help minimise damage and aid liver regeneration. Anti-emetic drugs and gastric protectant can also be used. Barrier nursing and strict hygiene are necessary to prevent spread of disease.
+In an outbreak
+*Isolate infected dogs
-A vaccine is available for infectious canine hepatitis and is a "core" canine vaccine. The vaccine is a modified live strain of CAV-2, which confers cross-protection against CAV-1. The primary course consists of two vaccinations given three to four weeks apart, and boosters are required at least every two to three years
+*Disinfect premises
+To prevent
+*'''Vaccination''': tissue culture adaptation that may be live or inactivated
+*Cross protection with CAV2
+*Live vaccines are known to cause keratitis in Afghans, Red Setters and Saluki
 ==Prognosis==
-Peracute cases carry a very poor prognosis and die within hours. The prognosis for acute cases is variable from guarded to good. It is also possible that recovered patients may develop chronic renal or hepatic disease.
-{{Learning
-|literature search = [http://www.cabdirect.org/search.html?start=0&q=%28%28%28diagnosis%29+OR+%28treatment%29%29%29+AND+%28%28title%3A%28%22Canine+Adenovirus+1%22%29+OR+%28%22Infectious+Canine+Hepatitis%22%29%29%29 Infectious Canine Hepatitis diagnosis and/or treatment]
-}}
 ==References==
-#Merck & Co (2008) '''The Merck Veterinary Manual (Eighth Edition)''' ''Merial''
-#Tilley, L.P. and Smith, F.W.K.(2004)'''The 5-minute Veterinary Consult (Third edition)''' ''Lippincott, Williams & Wilkins''.
-#Carter, GR and Wise, DJ (2005) '''A Concise Review of Veterinary Virology''', ''International Veterinary Information Service''.
-{{review}}
-{{OpenPages}}
-[[Category:Hepatitis, Viral]][[Category:Liver Diseases - Dog]]
-[[Category:Expert_Review]]
+[[Category:Hepatitis, Viral]][[Category:Dog]][[Category:To_Do_-_Clinical]]
+[[Category:To_Do_-_Lizzie]]