History
A 3-week-old male French Bulldog was submitted for necropsy after sudden death with no history of previous clinical disease. The affected puppy had 2 other siblings in the same litter. According to the referring veterinarian, 1 of the 2 remaining puppies had also died suddenly with no evidence of clinical disease. The third dog remained healthy.
Clinical and Gross Findings
Gross findings in the necropsied dog included disseminated, dark red, irregular foci of hemorrhage ranging from 1 to 3 mm in diameter distributed throughout the gastrointestinal serosa and pulmonary pleural surface as well as on the hepatic and renal capsular and cut surfaces (Figure 1). No other gross changes were observed.
Photographs of the abdominal cavity (A) and kidneys (B) of a 3-week-old male French Bulldog that died suddenly. Multifocal to coalescing, dark red areas of hemorrhage are present throughout the intestinal serosa and renal capsular surface.
Citation: Journal of the American Veterinary Medical Association 245, 6; 10.2460/javma.245.6.639
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic and Laboratory Findings
Microscopically, there were disseminated, well-demarcated areas of coagulative necrosis and hemorrhage in the stomach, intestines, lungs, liver, kidneys, spleen, lymph nodes, and adrenal glands. Necrotic foci in all of these organs were characterized by accumulations of hypereosinophilic cellular and nuclear debris admixed with extravasated erythrocytes, fibrin, and a few neutrophils. The multifocal areas of renal necrosis were associated with extensive interstitial hemorrhage and accumulations of neutrophils and fewer lymphocytes and plasma cells admixed with fibrin (Figure 2). Similarly in the liver, multifocal areas of hepatocellular necrosis were composed of accumulations of cellular and nuclear debris associated with hemorrhage and a few scattered neutrophils (Figure 3). Intranuclear eosinophilic viral inclusions were easily observed in hepatocytes at the margins of necrotic foci and less often in splenic macrophages. Additional findings included cerebral perivascular infiltration by a small number of lymphocytes and plasma cells in the neuropil and leptomeninges. Results of a fluorescent antibody test performed on fresh kidney and liver samples were positive for canine herpesvirus-1 (CHV-1).
Photomicrograph of a section of kidney tissue from the dog in Figure 1 containing extensive areas of coagulative necrosis (arrows) and hemorrhage (arrowheads). H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 245, 6; 10.2460/javma.245.6.639
Photomicrographs of a section of liver tissue from the dog in Figure 1. A—A focal and well-demarcated area of hepatocellular necrosis and hemorrhage (center) is admixed with cellular and nuclear debris and a few neutrophils. H&E stain; bar = 50 μm. B—Higher magnification reveals a hepatocyte (located at the margin of a necrotic focus [top left]) that contains an intranuclear eosinophilic viral inclusion (arrow) attributable to CHV-1. H&E stain; bar = 25 μm.
Citation: Journal of the American Veterinary Medical Association 245, 6; 10.2460/javma.245.6.639
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: disseminated coagulative necrosis and hemorrhage (stomach, intestine, lungs, liver, kidneys, spleen, lymph nodes, and adrenal glands) with intranuclear eosinophilic viral inclusions due to CHV-1 infection.
Case summary: CHV-1 infection in a 3-week-old dog that died suddenly.
Comments
The signalment, clinical history, and gross and microscopic findings in the case described here were typical of CHV-1 infection in young dogs.1,2 The diagnosis was confirmed by herpesviral antigen detection with a fluorescent antibody test on fresh kidney and liver tissue samples. Canine herpesvirus-1 is a DNA virus that can cause a fatal necrotizing disease in newborn puppies or nonspecific clinical syndromes in adult, often immunosuppressed dogs.1,2 Natural infection and clinical disease attributable to CHV-1 infection have only been described for domestic and wild canids, and the virus is maintained in nature by persistently infected canine hosts.1 Viral infection occurs mainly by direct contact with infected individuals, with prenatal or perinatal infection occurring occasionally.1,3 After primary viral replication in epithelial cells at the site of entry, affected individuals can develop clinical disease or become latently infected and remain without clinical signs. Viral latency may occur in various anatomic locations, including tonsils, retropharyngeal lymph nodes, respiratory and reproductive tracts, and trigeminal ganglia.3,4 Latently infected dogs are a source of CHV-1 for other susceptible individuals; viral reactivation and shedding usually occur following periods of stress in dogs with latent infection.1,3
Although the case described in the present report involved a 3-week-old dog, the clinicopathologic findings were typical of those described for the classic systemic necrotizing disease caused by CHV-1 infection in newborn puppies.1,2,5 This syndrome usually affects newborn or growing dogs < 2 weeks of age because these dogs are susceptible to infection owing to an incompletely developed homeothermic mechanism that facilitates viral replication under slightly lower body temperatures.1,2,5 Although infected puppies usually die suddenly, as did the one of this report, some individuals can develop nonspecific clinical signs such as lethargy, anorexia, signs of abdominal discomfort, diarrhea, mucosal petechial hemorrhages, cutaneous papules in the ventral aspect of the abdomen and the inguinal area, opisthotonos, and seizures.1,2,5 Necropsy findings in the case described in the present report reflected the changes typical of CHV-1 infection in very young dogs; such changes are usually characterized by disseminated areas of necrosis in several organs as well as pleural or peritoneal effusion.1,2,5 Microscopically, areas of coagulative necrosis are admixed with foci of hemorrhage with minimal or mild neutrophilic inflammatory response. The presence of intranuclear eosinophilic viral inclusions in epithelial cells and macrophages is highly suggestive of herpesviral infection in these cases.2,5
Clinical disease in dogs > 3 weeks of age or in adult dogs is uncommon and believed to be caused by concurrent infection or immunosuppression.1 In these older dogs, CHV-1 infection has been associated with mild or subclinical upper respiratory tract disease, infertility, abortion, and stillbirth.1,2 Although less commonly, CHV-1 infection has been associated with outbreaks of corneal ulcerations and with kennel cough syndrome in dogs.6,7
A presumptive diagnosis of CHV-1 infection may be made on the basis of the clinical history as well as the gross and microscopic findings, and diagnostic confirmation should be based on results of a fluorescent CHV-1–specific antibody test, viral isolation, or PCR assay.1,3,4 Treatment of puppies affected by systemic disease as a result of CHV-1 infection is usually unsuccessful because of the rapid and often fatal clinical course of the disease, but supportive care may be attempted.1 An inactivated CHV-1 vaccine for pregnant bitches is commercially available in Europe and has been shown to improve birth weight and weaning rate and to reduce the neonatal death rate associated with CHV-1 infection.8
An important differential diagnosis for CHV-1 infection in young dogs is canine adenovirus infection. Canine adenovirus-1 is responsible for infectious canine hepatitis and induces acute necrohemorrhagic hepatitis with intranuclear viral inclusions in hepatocytes and Kupffer cells that may resemble inclusions caused by CHV-1.9 Diagnostic differentiation between these infections is made on the basis of the gross and histopathologic findings and results of fluorescent antibody testing or PCR assay.1
References
1. Greene CE, Carmichael LE. Canine herpesvirus infection. In: Greene CE, ed. Infectious diseases of the dog and cat. 3rd ed. St Louis: Elsevier, 2006; 47–53.
2. Schlafer DH, Miller RB. Female genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's pathology of domestic animals. 5th ed. Philadelphia: Saunders-Elsevier, 2007; 526–528.
3. Burr PD, Campbell ME, Nicolson L, et al. Detection of canine herpesvirus 1 in a wide range of tissues using the polymerase chain reaction. Vet Microbiol 1996; 53: 227–237.
4. Miyoshi M, Ishii Y, Takiguchi M, et al. Detection of canine herpesvirus DNA in the ganglionic neurons and the lymph node lymphocytes of latently infected dogs. J Vet Med Sci 1999; 61: 375–379.
5. Carmichael LE, Squire RA & Krook L. Clinical and pathologic features of a fatal viral disease of newborn puppies. Am J Vet Res 1965; 26: 803–814.
6. Ledbetter EC, Riis RC, Kern TJ, et al. Corneal ulceration associated with naturally occurring canine herpesvirus-1 infection in two adult dogs. J Am Vet Med Assoc 2006; 229: 376–384.
7. Kawakami K, Ogawa H, Maeda K, et al. Nosocomial outbreak of serious canine infectious tracheobronchitis (kennel cough) caused by canine herpesvirus infection. J Clin Microbiol 2010; 48: 1176–1181.
8. Poulet H, Guigal PM, Soulier M, et al. Protection of puppies against canine herpesvirus by vaccination of the dams. Vet Rec 2001; 148: 691–695.
9. Stalker MJ, Hayes MA. Liver and biliary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's pathology of domestic animals. 5th ed. Philadelphia: Saunders-Elsevier, 2007; 348–351.
