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Equine multinodular pulmonary fibrosis: A newly described disease linked to EHV-5

Article

Equine Multinodular Pulmonary Fibrosis was only recently identified but could have a deep past.

Equine Multinodular Pulmonary Fibrosis (EMPF) is a disease identified only recently, but might it have been affecting horses undetected for a much longer time?

"I think that's an interesting question and I don't have an answer for it," says Kurt Williams, DVM, PhD, Dipl. ACVP, a pathologist at Michigan State University's College of Veterinary Medicine, where EMPF was identified earlier this year.

The disease was identified through case materials submitted to Williams, who works within the Department of Pathobiology and Diagnostic Investigation and is jointly appointed at MSU's Diagnostic Center for Population and Animal Health.

Working in collaboration with colleagues throughout the United States and Canada, Williams and researchers at MSU determined that EMPF should be considered a differential diagnosis for adult horses with interstitial pneumonia. Cases have been identified throughout the United States and in Canada.

The fibrotic lung disease is associated with lung infection with equine herpesvirus-type 5 (EHV-5), a gamma-herpesvirus that until now has not been associated with disease in horses.

According to Williams, his group's description of EMPF is "the first to document an association between a (naturally occurring) viral infection and lung fibrosis in any veterinary species, and the first to describe this disease. It (the EHV-5 virus) is extremely tightly associated with the development of the disease."

"That being said, we haven't proven causation yet. But I can tell you that in every horse that we have found the disease, if (it has) the characteristic pathology, we've been able to find the virus," Williams says.

But so far investigators haven't found evidence of the virus in the lungs in any of the control horses, those without EMPF.

Photo 1: Gross pathology of equine lung with EMPF. The foci of fibrosis (tan to off-white regions) in the lung of an EMPF-affected horse form readily identifiable nodules next to the unaffected lung (salmon-colored regions).

Since publication of the initial paper in Veterinary Pathology describing EMPF and its association with EHV-5, Williams and colleagues have had several more cases submitted to them for examination and testing. They've confirmed the close relationship between the virus and fibrotic lung lesions. "Essentially 100 percent of the animals that have the disease have the virus," Williams says.

An emerging disease?

Could EMPF have been around much longer but only now being recognized, or is it an emerging disease?

"It might be possible that we're seeing more (cases) because people are sensitized now," Williams says.

But there is one factor that makes him wonder if it's more than just a case of heightened awareness following publication:

"The pathology is so spectacular and characteristic, both the gross and histopathology, that part of me thinks this disease is such that somebody would have put this together if it had been out there for years and years," Williams says.

"It makes me wonder if maybe this disease really is starting to emerge. The clinical presentation is quite characteristic. If you talk to the equine medicine people, they note that it has very characteristic radiographic findings. And when we look at the pathology, it is spectacular, incredibly characteristic and severe."

The disease has been identified in adult horses of various ages (4-28), and of various breeds, including Thoroughbred, Arabian, Warmblood, Quarter Horse, Andalusian, Belgian, Westphalian, Oldgenburg and mixed-breed horses. According to Williams, EMPF has not been seen in young horses or foals thus far. "It appears to be a disease of adult horses," Williams says.

The signs associated with EMPF are severe respiratory distress, characterized by tachypnea, tachycardia, intermittent fever, cough, nasal discharge, decreased appetite, weight loss, thin body condition and lethargy.

Photo 2: Histopathology of equine lung with EMPF. The fibrosis within the lung (pink) replaces the normal lung tissue, leaving airspaces filled with inflammatory cells, and lined by cuboidal epithelial cells.

A marked inflammatory response often was detected in affected horses, Williams says.

Clinicopathologic abnormalities include anemia, lymphopenia and hypoxemia. Upon auscultation of the thorax, moderately increased bronchovesicular sounds were present bilaterally. Ventral crackles and bilateral wheezes were noted in some horses. In several affected horses, various lung sounds were detected upon auscultation, varying from normal sounds to increased or diminished bronchiovesicular sounds.

Thoracic radiography "revealed a severe, diffuse, uniformly distributed nodular interstitial pattern," Williams says, and "numerous discrete to coal-escing nodular densities were visible within the lungs."

Ultrasonic examination of the lungs "revealed multiple, well-defined, 1-2 cm nodular lesions on the surface of the lungs," he says.

The more common gross lesions were pale, tan to white nodules, moderately firm. The less common lesions were multiple discrete nodules, separated by grossly unaffected lung, which were larger than the coalescent form of the disease, up to 10 cm, also pale tan to white, firm with larger areas of normal lung between the nodules.

"Examination of tracheal and bronchial fluid aspirates consistently revealed purulent inflammation with nondegenerate to degenerate neutrophils," Williams says.

Histologically, the lesions of EMPF are centered on the alveolar parenchyma. "The nodules within the lung result from marked interstitial expansion with collagen-replacing alveoli. The adjacent alveoli are lined by cuboidal epithelial cells, and the lumen is filled with moderate numbers of neutrophils and macrophages," Williams explains.

"Nodules were sharply demarcated from adjacent, less affected lung. The nodules consisted of marked interstitial expansion by well-organized matured collagen. The interstitium was infiltrated by variable numbers of mixed inflammatory cells, consisting primarily of lymphocytes, with smaller numbers of macrophages, neutrophils and occasional eosinophils."

According to Williams, "The pattern of lung fibrosis, the paucity of viral inclusion bodies, and an incomplete general understanding of viral infections and tissue fibrosis may have contributed to this disease (EMPF) going unreported for some time."

The prognosis for horses with EMPF is considered fair to poor. Treatment is suggested for at least six weeks before evaluating efficacy of treatment and prognosis.

"Some antivirals and cortico-steroids have been tried with varying success," Williams notes.

But most of the animals don't respond well to therapy, he says.

A handful did respond to therapy, but there hasn't yet been a controlled study, so investigators don't know whether those few improving horses are getting better due to the therapy or because of other factors unique to them.

"Certainly there have been some animals that return to form," Williams says. "But if you wanted to paint it with a broad brush, it's a progressive disease, and most of the horses don't respond well to therapeutic intervention," he says.

Humans are afflicted with lung fibrosis, and there is some question as to the role that viral infections, in particular herpesviruses, play in pulmonary fibrosis in people.

"There is a lot of interest in human medicine regarding the role that viruses play in either initiating fibrotic lung diseases or in perpetuating fibrotic lung diseases," Williams says. "So, there is a broader interest, I think scientifically, from a comparative medicine standpoint. It does have broader ramifications potentially in helping us understand lung fibrosis in general and the role that viruses may or may not be playing in these diseases."

Whatever the case in the equine disease, and whatever relationship to human fibrotic lung disease may exist, there is one thing common to EMPF in horses:

"There are huge numbers of missing pieces to the puzzle," says Williams.

Kane is a Seattle author, researcher and consultant in animal nutrition, physiology and veterinary medicine, with a background in horses, pets and livestock.

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