Signalment:  

Two day old, male Thoroughbred, Equus caballus, equine.The colt presented at 9 hours of age with a history of premature placental separation at birth. Severe respiratory disease developed whilst the colt was hospitalized and worsened despite mechanical ventilation


Gross Description:  

The lungs are heavy and edematous, and mottled red purple. The most cranioventral portions have numerous air filled pockets under the pleura. Scattered on the pleural surface and also on cut section are multiple white, less than 3mm diameter, foci (figure 1). The pericardium is expanded by edema. The capsular surface and parenchyma of the liver contain randomly disseminated pinpoint to less that 3mm diameter white-gray foci (figure 1). The cortex of the adrenal glands contains scattered hemorrhagic foci. 


Histopathologic Description:

Within the lung, there is extensive necrosis of the respiratory epithelium, predominantly affecting bronchioles but also bronchi and terminal airways. Sloughed cells admixed with necrotic debris and inflammatory cells accumulate within the lumens. Both necrotic cells and viable epithelium contain eosinophilic nuclear inclusion bodies that peripheralize the chromatin (Cowdry type A), and there is formation of epithelial syncytia. Extending into alveoli (which are often necrotic) are accumulations of fibrin, neutrophils and macrophages. Type II pneumocytes are hyperplastic. Interlobular septa are edematous and contain an infiltrate of macrophages and neutrophils. 

Scattered randomly within the adrenal cortex are areas of congestion, hemorrhage and necrosis. Immediately adjacent to the cytoclastic debris are cells that contain eosinophilic nuclear inclusion bodies that peripheralize the chromatin.

Equine herpesvirus 1 (EHV-1) antigen was detected by immunohistochemisty within the nucleus and cytoplasm of several epithelial cells and leukocytes in the lung (figure 2) and adrenal gland (figure 3). Appropriate positive and negative controls were used and examined and worked accordingly.


Morphologic Diagnosis:  

Lung: bronchointerstitial pneumonia, necrotizing, acute, diffuse, severe with eosinophilic nuclear inclusion bodies and epithelial syncytia.
Adrenal gland: adrenalitis, necrotizing, acute, multifocal, moderate with eosinophilic nuclear inclusion bodies.


Lab Results:  

Virus isolation performed on lung, liver, kidney, spleen and thymus was positive for EHV-1 and negative for EVA. FA performed for EHV-1 antigens on lung and liver was also positive, and EVA FA was negative. Aerobic culture of the lung produced no growth. Leptospira was not detected in the lung, liver, spleen and kidney by FA. 


Condition:  

Equine herpesvirus-1


Contributor Comment:  

Equine herpes virus 1 is an alphaherpes virus, responsible for causing abortion, perinatal foal mortality, respiratory disease and neurologic disease in horses7. Due to its direct effect on breeding and performance, and also through interference with horse movement, EHV-1 is of major economic and welfare importance in horse related industries throughout the world3. Pregnant mares exposed to infection abort three weeks to four months after exposure to infection. Abortion occurs anytime after five months gestation, but more commonly from nine months to term. Foals may be born alive, as in this case, but death occurs within a few days4,11. 

The pathogenesis of EHV-1 abortion is not fully elucidated11. Virus is translocated from the maternal circulation to the uterus and placenta. Uterine lesions consist of vasculitis in the small arterioles of the endometrium11. In some cases, abortion can occur without fetal lesions or virus spread to the fetus, presumably from widespread virus-related thrombosis and infarction leading to premature placental separation and expulsion of the fetus14. Placental lesions in these cases consist of chorionic necrosis and fibrinoid vascular necrosis of chorionic blood vessels with fibrin thrombi13,14. EHV-1 has been detected in endometrial and chorionic endothelial cells in experimental and spontaneous cases of abortion by ISH and immunohistochemistry12,13,15.

More commonly virus spreads to the fetus. In addition to placental endothelial cells, DNA ISH also has identified EHV-1 in necrotic debris associated within infarcted microcotyledons, debris within endometrial glands and also trophoblasts, suggesting trophoblast infection results from diffusion of virus from sites of endometrial infarction and also from emptying of debris from infected glands directly onto the surface of trophoblasts12. 

EHV-1 infection of the fetus results in well described and documented lesions. Grossly, the aborted fetus is usually fresh with subcutaneous edema and petechiae of the mucous membranes. The lungs are edematous and the trachea may contain a fibrinous cast. The liver contains miliary white foci of necrosis. The spleen may contain prominent lymphoid follicles2,9. Histologic lesions consist of necrosis and eosinophilic intranuclear inclusion bodies in parenchymal organs, especially the liver and adrenal glands, with minimal inflammatory cell infiltrate, lymphocytolysis in the thymus and bronchointerstitial pneumonia2,6. Syncytia formation in EHV-1 infection, as seen in this case, is rarely described. Previous reports include syncytia in the lungs of aborted fetuses6 and in experimental neurologic disease3. 


JPC Diagnosis:  


1. Lung: Pneumonia, bronchointerstitial, necrotizing, acute, multifocal, moderate, with fibrin, edema, syncytia, and eosinophilic intranuclear inclusion bodies, Thoroughbred (Equus caballus).
2. Adrenal gland, cortex: Necrosis, multifocal, with rare eosinophilic intranuclear inclusion bodies.


Conference Comment:  

The contributor includes an excellent review of EHV-1 associated abortions. EHV-1 is transmitted primarily through the respiratory system. Following an initial replication in the upper respiratory mucosal epithelium, the virus is transmitted throughout the body via mononuclear cells, primarily T-lymphocytes. Horses are latently infected for life.

There are three types of Equine Alphaherpes viruses:
EHV-1 and EHV-4 both can cause abortion, although it occurs more often with EHV-1. EHV-1 and EHV-4 both can cause respiratory disease, although it is more common with EHV-4.

Slide variation includes some slides with syncytia in the adrenal cortex.


References:

1. Caswell JL, Williams KJ: Respiratory system. In: Maxie MG, Youssef S: Nervous system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 4th ed., vol. 2, p. 629. Elsevier Limited, St. Louis, MO, 2007
2. Foster RA: Female Reproductive System. In: Pathologic Basis of Veterinary Disease, ed. Mc Gavin MD, Zachary JF, 4th ed., pp1298-1299. Mosby Elsevier, St Louis, Missouri, 2007
3. Jackson TA, Osburn BI, Cordy DR, Kendrick JW: Equine herpesvirus 1 infection of horses: studies on the experimentally induced neurologic disease. Am J Vet Res 38: 709-719, 1977
4. LeBlanc, MM: Abortion. In: Equine Medicine and Surgery, Volume II, eds. Colahan PT, Mayhew IG, Merritt AM, Moore JN, 5th ed., pp1205-1206. Mosby St Louis, Missouri 1999
5. Maxie MG, Youssef S: Nervous system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 4th ed., vol. 1, pp. 431-431. Elsevier Limited, St. Louis, MO, 2007
6. Mukaiya R, Kimura T, Ochiai K, Wada R, Umemura T: Demonstration of Equine Herpesvirus-1 gene expression in the placental trophoblasts of naturally aborted equine fetuses. J com Path 123:119-125, 2000
7. Murphy FA, Gibbs EPJ, Horzinek MC, Studdert MJ: Veterinary Virology, pp 301-303. Academic Press, San Diego, California, 1999
8. Paradis MR: Equine respiratory viruses. In: Large Animal Internal Medicine, ed. Smith BP, 2nd ed., pp. 587-588, Mosby, St. Louis, MO, 1996
9. Rooney JR, Robertson JL: Equine Pathology pp 246-248. Iowa State University Press, Ames, Iowa, 1996
10. Schlafer DH, Miller RB: Female genital system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 4th ed., vol. 3, pp. 532-533, Elsevier Limited, St. Louis, MO, 2007
11. Slater J: Equine Herpesviruses. In: Equine Infectious Diseases, eds. Sellon DC, Long MT, 1st ed., pp 134-145. Saunders Elsevier, St Louis, Missouri, 2007
12. Smith KC, Borchers K: A study of the pathogenesis of Equid Herpesvirus-1 (EHV-1) abortion by DNA in-situ hybridization. J comp Path 125:304-310, 2001
13. Smith KC, Mumford, JA, Lakhani K: A comparison of Equine Herpesvirus-1 (EHV-1) vascular lesions in the early versus late pregnant equine uterus. J Comp Path 114:231- 247, 1996
14. Smith KC, Whitwell KE, Blunden AS, Bestbier ME, Scase TJ, Geraghty RJ, Nugnet J, Davis-Poynter NJ, Cardwell JM: Equine herpesvirus-1 abortion: atypical cases with lesions largely or wholly restricted to the placenta. Equine Vet J 36:79-82, 2004
15. Szeredi L, Aupperle H, Steiger K: Detection of Equine Herpesvirus-1 in the fetal membranes of aborted equine fetuses by immunohistochemical and in-situ hybridization techniques. J Comp Path 129:147-153, 2003

A virtual slide is not available for this case.


Liver and lung, horse


Lung, horse


Figure 3


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