Theiler’s disease, also known as equine serum hepatitis, is a viral infection likely caused by equine parvovirus-hepatitis. Horses most commonly develop Theiler’s disease after administration of an equine-origin biologic product, such as serum or blood.

Theiler’s disease causes rapid onset liver failure, with symptoms such as yellowing of the gums and whites of the eyes (jaundice), colic, fever, and uncoordinated movement. Veterinarians may use a combination of bloodwork, ultrasound, and liver biopsy to identify the cause of liver failure.

Treatment is primarily supportive, involving intravenous fluids, sedation, antibiotics, and dietary changes. The prognosis varies, with severely affected horses having a poor to grave prognosis. Less severely affected horses may recover completely.

Equine parvovirus-hepatitis is a recent discovery, and ongoing research aims to determine the routes of exposure, risk factors, and best treatment options for this virus.

Thelier’s Disease in Horses

Research suggests Theiler’s disease is likely caused by equine parvovirus-hepatitis (EqPV-H). [1]

Historically, the cause of Theiler’s disease was unknown. [2] The name “equine serum hepatitis” arose from the finding that most horses with Theiler’s disease had received a biologic antiserum. [2]

These treatments are derived from the blood of healthy horses and provide additional antibodies against a target disease when administered intravenously to unhealthy horses. [2]

This finding led many researchers to suggest the cause of Theiler’s disease was an unknown infectious agent, transmitted in the blood. [1][2]

In 2018, researchers identified a parvovirus, equine parvovirus-hepatitis, in numerous cases of Theiler’s disease. [1][3] Affected cases with equine parvovirus-hepatitis also included horses who had not received a biologic. [4]

Research into EqPV-H is ongoing, and aims to identify how the disease spreads between horses. [5]

Asymptomatic Horses

Since its discovery, researchers have identified equine parvovirus-hepatitis in many horses showing no symptoms. [1] Estimates suggest that between 7-17% of horses carry the virus. [1] There are reported asymptomatic cases from the United States, China, Germany, and Austria. [1]

Asymptomatically infected horses may contribute to producing parvovirus-contaminated biologic products, which then transmit the disease to other horses. [1] Equine serum products from New Zealand, the United States, Italy, Germany, and Canada showed a 61% positivity rate for EqPV-H. [1]

These horses may also be a source of infection outside of the use of biologics if other infectious routes are identified. [1] Studies show that EqPV-H carriers can shed the virus in nasal, oral, and fecal products. [4]

One experimental attempt at infecting a horse through ingestion of the bacteria was successful, indicating a possible oral route of infection. [4]

Currently the significance of asymptomatic infection in affected horse is unknown. [1] It appears only a low percentage of infected horses develop symptoms of Theiler’s disease. [5] Specific risk factors for which horses develop disease from EqPV-H infection are currently unknown. [1]

Risk Factors

The major risk factor for Theiler’s disease development is previous administration of an equine biologic product. [2] Most of these products are antisera given to treat a specific disease. [2]

Diseases that may involve antisera in their treatment protocols include: [2]

Cases of Theiler’s disease have also been reported after administration of plasma or other blood products to sick horses. [1] In 2019, the United States Department of Agriculture placed regulations on equine biologic products requiring that all products be tested for EqPV-H prior to use. [1]

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Other Routes of Infection

Although most cases of Theiler’s disease arise from administration of a biologic antiserum, there are several reports of cases in horses who did not receive a biologic. [1] Most of these cases occurred during the summer and autumn, suggesting insect-based transmission may be possible. [1]

Additionally, studies show that horses in contact with affected horses have a higher risk of developing Theiler’s disease themselves. [1] Prevalence rates of EqPV-H carriers ranges from 51 – 61% on farms with a previous case of Theiler’s disease, which is much higher than on unaffected farms. [5]

All of these findings suggest that EqPV-H may be contagious, although the precise mechanism of contagious spread is currently unknown. [1] Currently proposed mechanisms of spread include: [1][6][7]

  • Equine biologic products
  • Sharing needles, rectal sleeves, stomach tubes, or dental equipment which may contact blood
  • Biting flies
  • Nasal contact with the virus
  • Ingestion of the virus

Symptoms

Theiler’s disease is most common in adult horses. [2] Symptoms usually develop rapidly and progressively worsen over 2 – 7 days. [2]

General symptoms of liver failure are characteristic of equine serum hepatitis and may include: [2]

  • Reduced appetite
  • Yellowing of the gums and whites of the eyes (jaundice)
  • Uncoordinated movement (ataxia)
  • Swelling of the lower neck, chest, and abdomen
  • Fever
  • Colic
  • Lethargy
  • Persistent yawning
  • Weight loss

Horses with Theiler’s disease may develop a syndrome called hemorrhagic diathesis. [2] Since the liver is responsible for producing the proteins used in blood clotting, liver failure often results in fewer clotting proteins available to form blood clots. [2]

Symptoms of hemorrhagic diathesis include: [2]

  • Multiple small hemorrhages on the gums
  • Failure of blood to clot after injections
  • Spontaneous bleeding from the nose
  • Red urine
  • Dark black feces

Some horses with Theiler’s disease die suddenly with few to no prior symptoms. [2]

Diagnosis

There are several diseases of the liver that can cause similar symptoms to Theiler’s disease.

Diagnostics that veterinarians may perform to identify the cause of liver disease include: [2]

  • Bloodwork
  • Ultrasound of the liver
  • Liver biopsy

Other diagnoses that a veterinarian may consider include: [2]

Typically, a liver biopsy is necessary to diagnose Theiler’s disease, as the results of other diagnostic tests can be non-specific. [2] However, a history of receiving an equine-origin biologic treatment leading up to the onset of symptoms is usually enough to make a tentative diagnosis of Theiler’s disease. [2]

The recent discovery of equine parvovirus-hepatitis means that less invasive diagnostic tests identifying the viral genetic sequence will likely become available in the future. [1]

Bloodwork

Bloodwork is a critical component of diagnosing liver disease in horses. [2] Levels of different metabolites in the blood indicate whether the liver is processing these products correctly, and gives the veterinarian an overview of the liver’s function. [2]

Common metabolites analyzed include: [2]

  • Bilirubin: byproduct that forms when the body recycles red blood cells. Normally, the liver excretes bilirubin in the bile. In liver failure, bilirubin levels increase due to decreased excretion.
  • Bile acids: the digestive tract reabsorbs bile acids for reuse in the bile after processing by the liver. Increased bile acids in the bloodstream indicates decreased liver processing.
  • Proteins: the liver is responsible for producing many proteins in the body, including proteins involved in blood clotting. Decreased protein in the blood can indicate liver failure.
  • Ammonia: degradation of proteins for use as an energy source produces ammonia, which is processed by the liver. Higher levels of blood ammonia can occur during liver disease.
  • Liver enzymes: liver damage can cause the release of enzymes normally found within the liver into the bloodstream. Increased levels of these enzymes indicates damage at the cellular level within the liver.

Ultrasound

Veterinarians use ultrasound to evaluate the shape and structure of the liver. [2] This imaging modality can identify any unusual structures within the liver, such as abscesses, cysts, or tumours. [2] It can also identify bile duct obstructions that can cause damage. [2]

Ultrasound findings associated with Theiler’s disease include a shrunken, small liver that may be difficult to visualize. [8]

Liver Biopsy

Liver biopsy is currently the gold standard for diagnosis of Theiler’s disease in horses. [2] Veterinarians can biopsy the liver through the skin (transcutaneous) or during an abdominal surgery. [2]

To perform a transcutaneous biopsy, the area between the 12th and 14th ribs is clipped and surgically prepared. [2] The veterinarian injects a local anesthetic, such as lidocaine, into the area and makes a small incision with a scalpel blade. [2] They insert a biopsy needle through the incision and into the liver. [2]

Veterinarians submit liver biopsies to a diagnostic laboratory for evaluation. [2]

Signs of Theiler’s disease on a biopsy include: [2]

  • Widespread death of liver cells
  • Swelling of liver cells indicating poor processing of metabolites
  • Mild inflammatory changes

Necropsy

Horses with Theiler’s disease may die before the cause of their liver disease is identified. [2] Veterinarians may perform a necropsy (autopsy) on the horse to better understand the cause of death. They can also take samples of the liver during the necropsy for submission to a diagnostic lab.

The characteristic finding of Theiler’s disease on necropsy is a “dishrag” liver. [9] Rather than a firm liver texture that holds its shape, the liver is soft and thin, similar to a dishrag. [9] This finding is highly suggestive of Theiler’s disease, and reflects the large amount of liver cell death that occurs in this disease.

Treatment

Treatment for Theiler’s disease is primarily supportive, with the goal of maintaining the horse until liver function recovers. [2]

Supportive care may involve: [2]

  • Sedation
  • Intravenous fluids
  • Antibiotics
  • Dietary changes

Sedation

Many horses with Theiler’s disease develop hepatic encephalopathy, a condition where inadequate processing of ammonia in the bloodstream by the liver allows ammonia levels to rise. [2]

Ammonia causes loss of ATP, the primary source of cellular energy, within nerves. [2] This can result in cell death and damage to the central nervous system. [2]

Horses with hepatic encephalopathy often display unusual behaviors such as restlessness and agitation. [2] They also have uncoordinated movement and are prone to falling down or collapsing. [2]

For these reasons, veterinarians often sedate horses with hepatic encephalopathy to keep them calm and allow for safe handling. [2]

Intravenous Fluids

The liver has an essential role in maintaining fluid balance and electrolyte levels within the bloodstream. [2] During liver failure, compromise of these functions requires ongoing management by the veterinary team to restore normal blood values. [2]

Veterinarians use intravenous fluids, often combined with electrolyte preparations, to correct these blood changes. [2]

Antibiotics

Bacteria in the intestine produce high levels of ammonia, and are a potential source of ammonia in hepatic encephalopathy. [2]

Veterinarians may use antibiotics, like neomycin, to change the intestinal microflora by removing ammonia-producing bacteria. [2]

This can help control symptoms of hepatic encephalopathy by reducing the ammonia burden in the bloodstream. [2]

Dietary changes

Low protein diets can also help control ammonia levels in the blood. [2] Breakdown of proteins in the body’s tissues is a major source of ammonia that would typically be removed by a healthy liver. [2]

Feeding a low protein diet can prevent cells from using protein as an energy source, thus reducing the amount of ammonia produced. [2]

Prognosis and Prevention

The prognosis for Theiler’s disease in horses depends on the severity. Horses that develop signs of hepatic encephalopathy or hemorrhages throughout the body have a poor to grave prognosis. [2]

Most horses that survive longer than 1 week after the development of symptoms make a full recovery. [2] However, there are occasional reports of sudden death or progressive weight loss months after recovering from Theiler’s. [2]

Currently, the only known preventative measure for Theiler’s disease is careful use of equine-origin biologics. [2]

These products should only be used in severe cases of disease where the horse is unlikely to survive without these treatments. [2] Additionally, equine biologics should be screened for EqPV-H prior to use. [1]

Summary

Theiler’s disease in horses is a viral infection associated with equine parvovirus-hepatitis infection.

  • Most horses develop Theiler’s disease after administration of an equine-origin biologic product
  • The virus can cause rapid onset liver failure that horses may not recover from
  • Symptoms include yellow gums and whites of the eyes, colic, fever, and uncoordinated movement
  • Bloodwork, ultrasound, and liver biopsies are the main diagnostics for liver disease
  • There is no specific treatment available for Theiler’s disease
  • The prognosis depends on the severity of disease, with some horses having a poor to grave prognosis
  • Research into equine parvovirus-hepatitis is ongoing

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References

  1. Ramsauer, A. S. et al., Equine Parvovirus Hepatitis. Equine Veterinary Journal. 2021.View Summary
  2. Reed, S. M. et al., Equine Internal Medicine. 3rd ed. Saunders Elsevier, St. Louis, Mo. 2010.
  3. Tomlinson, J. E. et al., Viral Testing of 18 Consecutive Cases of Equine Serum Hepatitis: A Prospective Study (2014‐2018). Journal of Veterinary Internal Medicine. 2019. View Summary
  4. Tomlinson, J. E. et al., Viral Testing of 10 Cases of Theiler’s Disease and 37 in-Contact Horses in the Absence of Equine Biologic Product Administration: A Prospective Study (2014-2018). Journal of Veterinary Internal Medicine. 2019. View Summary .
  5. Divers, T. J. et al., The History of Theiler’s Disease and the Search for Its Aetiology. The Veterinary Journal. 2022. View Summary
  6. Tomlinson, J. E. et al., Tropism, Pathology, and Transmission of Equine Parvovirus-Hepatitis. Emerging Microbes & Infections. 2020.
  7. Tomlinson, J. E. et al., What Do We Know About Hepatitis Viruses in Horses?. Veterinary Clinics of North America: Equine Practice. 2019. View Summary
  8. Foreman, J., Acute Hepatitis in Large Animals – Digestive System. Merck Veterinary Manual.
  9. Maxie, M. G., Ed., Jubb, Kennedy & Palmer’s Pathology of Domestic Animals. Volume 2. Sixth edition. Elsevier, St. Louis, Missouri. 2016.