10-year-old female equine Thoroughbred (Equus caballus)The mare had signs of equine protozoal myeloencephalitis (EPM) then developed pneumonia. The mare responded to EPM therapy but had continuing weight loss and cachexia despite a variety of treatments for pneumonia. The mare was euthanized due to continued loss of body condition.

Gross Description:  

Significant changes were restricted to the lungs. Bilaterally, lung lobes were diffusely firm and failed to collapse when the thoracic cavity was opened. Throughout the pulmonary parenchyma were multifocal to coalescing firm, light pink, irregularly round nodules that varied in size from 1cm to large confluent masses. The nodules were separated by normal appearing tissue. When sectioned, the masses had a firm fibrous texture and bulged slightly on cut surface. 

Histopathologic Description:

Sections of lung are characterized by multifocal areas of pulmonary fibrosis and inflammation bordered by more normal appearing lung tissue. Alveolar septa are moderately to severely expanded by well organized mature collagen (Fig. 2-1). Alveoli are often lined by plump cuboidal cells (Type 2 pneumocyte hyperplasia), and alveolar lumens contain a mixture of sloughed epithelial cells, intact and degenerate neutrophils, large foamy macrophages, and few multinucleated giant cells. Rare macrophages contain large, brightly eosinophilic, round, intranuclear inclusion bodies that peripheralize nuclear chromatin and are occasionally surrounded by a clear halo (Fig. 2-2). 

Morphologic Diagnosis:  

Severe multifocal nodular fibrosing interstitial pneumonia with intranuclear inclusion bodies, Equus caballus; Equine multinodular pulmonary fibrosis

Etiology: Equine Herpesvirus-5 (EHV-5)


Equine multinodular pulmonary fibrosis

Contributor Comment:  

Equine multinodular pulmonary fibrosis (EMPF) is a distinct entity in the category of equine chronic pulmonary disease. It is differentiated from other fibrosing inflammatory diseases, such as recurrent airway obstruction (RAO) or chronic pneumonia, by the nodular pattern of fibrosis. This disease may have been previously reported under the names idiopathic interstitial pneumonia with fibrosis or idiopathic pulmonary fibrosis.

EMPF is most common in middle-aged horses. Horses with this disease present with non-specific signs of respiratory disease including cough, fever, weight loss, tachypnea, increased respiratory effort, and nasal discharge. Treatment with antibiotics may result in short-term improvement, but symptoms recur after treatment is discontinued. Pulmonary nodules can be visualized with ultrasonography and/or radiography. Rule outs include neoplasia, fungal pneumonia, and granulomatous pneumonia, which may also result in a nodular pattern. Treatment of choice includes long-term (at least 6 weeks) administration of corticosteroids. Prognosis for the disease is considered fair to poor. Many horses are euthanized due to continued respiratory complications and poor athletic performance.

Lung tissue from this horse was positive via polymerase chain reaction (PCR) for EHV-5. EHV-5 is a DNA gammaherpes virus that has only recently been associated with this disease entity. The pathogenesis of EHV-5 in this disease has not been fully elucidated but may contribute to a pro-fibrotic lung environment via a Th-2 lymphocyte inflammatory response. PCR can be performed on bronchoalveolar lavage samples or lung tissue. Unlike EHV-2, another common viral cause of equine respiratory disease, EHV-5 is not isolated from healthy horses or horses with respiratory disease due to other etiologies. A study by Bell identified EHV-5 in 64% of young racehorse nasal swabs, while a study performed by Wang identified the virus in 48% of 5-9 month old Thoroughbred foals. 

Intranuclear inclusion bodies are not a common feature in gammaherpes infections but may be observed in California sea lions infected with genital carcinoma caused by gammaherpes virus. Murine herpesvirus-68 is a gamma herpesvirus associated with experimental fibrotic lung disease in mice.

JPC Diagnosis:  

Lung: Fibrosis, interstitial, nodular, multifocal, severe with neutrophilic and histiocytic alveolitis, type II pneumocyte hyperplasia and rare intrahistiocytic eosinophilic intranuclear inclusions

Conference Comment:  

There are several alpha herpesviruses that are of significance in domestic animals. Listed below are some of the major alpha herpesviruses of significant importance in veterinary medicine. 
Alpha herpesvirusDisease
Equine herpesvirus 1 Abortion, foal mortality, neurologic and respiratory disease
Equine herpesvirus 3 Coital exanthema
Equine herpesvirus 4 Rhinopneumonitis
Bovine herpesvirus 1 Infectious bovine rhinotracheitis, infectious pustular vulvovaginitis
Bovine herpesvirus 2 Bovine mammilitis, pseudo-lumpyskin disease
Porcine herpesvirus 1 (pseudorabies; Aujeszky's Disease) Abortion in adults and generalized disease in younger animals; death in other species
Canine herpesvirus 1 Pneumonia, hepatitis, nephritis hemorrhagic disease
Feline herpesvirus 1 Feline viral rhinotracheitis
Gallid herpesvirus 1 (chickens) Infectious laryngotracheitis
Gallid herpesvirus 2 (chickens) Mareks disease
Anatid herpesvirus 1 Duck plague
Cercopithecine herpesvirus 1 (B virus) Herpes simplex-like disease in macaques; encephalitis and death in humans



1. Murphy FA, Gibbs EPJ, Horzinek MC, Studdert MJ: Herpesviridae: In: Veterinary Virology, eds. Murphy FA, Gibbs EPJ, Horzinek MC, Studdert MJ, 3rd ed., pp. 301-325. Academic Press, San Diego, California, 1999
2. Williams KJ, Maes R, Del Piero F, Lim A, Wise A, Bolin DC, Caswell J, Jackson C, Robinson NE, Derksen F, Scott MA, Uhal BD, Li X, Youssef SA, Bolin SR: Equine multinodular pulmonary fibrosis: a newly recognized herpesvirus-associated fibrotic lung disease. Vet Pathol 44(6):849-62, 2007
3. Wong DM, Belgrave RL, Williams KJ, Del Piero F, Alcott CJ, Bolin SR, Marr CM, Nolen-Walston R, Myers RK, Wilkins PA: Multinodular pulmonary fibrosis in five horses. J Am Vet Med Assoc 15:898-905, 2008

Click the slide to view.

2-1. Lung, horse.

2-2. Lung, horse.

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