Immune-mediated myositis (IMM) is a muscle disorder in horses where the immune system mistakenly attacks its own muscle fibers, resulting in severe muscle atrophy. [1]

IMM is one of the two disorders classified under Myosin Heavy Chain Myopathy (MYHM) in horses. These diseases are associated with mutations in the myosin heavy chain 1 (MYH1) gene. [1]

The main symptoms of IMM are severe, rapid muscle loss and stiffness. Several other muscle disorders can cause similar symptoms, so diagnosis requires a thorough work-up by a veterinarian. Definitive diagnosis of IMM requires a muscle biopsy or genetic test.

There is no treatment for IMM and affected horses may have multiple episodes of symptoms throughout their life. Managing an episode may involve corticosteroids, pain medications, and muscle relaxants.

This condition is most commonly observed in Quarter Horses and related breeds, but it can affect any horse. IMM is preventable by genetic testing prior to breeding. Currently, genetic testing is only recommended, but not required, by the American Quarter Horse Association.

Immune Mediated Myositis in Horses

Immune-mediated myositis in horses results from a mutation in the myosin heavy chain 1 gene (MYH1). [1] This mutation affects fast-twitch muscle fibers, which are most highly concentrated in the muscles of the hind limbs and back. [2]

The MYH1 mutation causes muscle fibers to have an abnormal structure, predisposing them to disease. [1] In IMM, the horse’s own immune system attacks the abnormal muscle tissue, resulting in rapid muscle degeneration. [1][4]

Despite carrying the MYH1 mutation, horses typically do not develop IMM without a “triggering event” that activates the immune system in such a way that it attacks its own fast-twitch muscle fibers. [4] The first signs of IMM usually develop 3-4 weeks after the triggering event. [4]

The precise trigger of immune-mediated myositis is usually unknown in most cases. [1] Previously reported triggering factors include: [1]

Triggering Events

Although MYHM disorders are not fully understood, it seems likely that infections trigger IMM due to similarities between the structure of bacteria or viruses and the abnormal muscle fibers. [4]

When the immune system encounters bacteria or viruses, it targets and destroys all tissues with a similar structure in an effort to resolve the infection. [4] If the abnormal changes in the muscle make them resemble the structure of these pathogens, they may be destroyed in error as part of the immune response. [4]

Vaccinations are also a potential trigger of IMM in genetically predisposed horses. Vaccines may trigger IMM following a similar mechanism as infections, or may occur due to the intramuscular injection process itself. [4]

Intramuscular injections can cause small amounts of muscle damage at the injection site, which could alert the immune system to the presence of abnormal muscle fibers. [4] After activation, the immune system might target these muscle fibers for destruction, leading to IMM. [4]

Nonexertional Rhabdomyolysis

Nonexertional rhabdomyolysis is the other disease under the myosin heavy chain myopathy umbrella, and may also occur in horses affected by IMM. In some horses, an episode of nonexertional rhabdomyolysis may be the triggering event for IMM to develop. [1]

Nonexertional rhabdomyolysis is sometimes described as “tying up not caused by exercise“, distinguishing this condition from exertional rhabdomyolysis.

Rhabdomyolysis describes the breakdown of skeletal muscle, resulting in release of muscle proteins into the bloodstream. [1] Muscle proteins are highly toxic to the kidneys, and can rapidly cause kidney failure. [1]

The MYH1 mutation appears to affect the binding of myosin to actin, the two major proteins in muscle fibers. [3] These two linear proteins run parallel to each other within the muscle fiber. [3]

During normal muscle contraction, myosin attaches to actin and “crawls” along the actin filaments, causing the muscle fibers to shorten. [3] When the muscle relaxes, the myosin protein detaches completely, allowing the muscle to return to its original length. [3]

Research into muscle function shows the MYH1 mutation causes stronger attachment between the actin and myosin proteins. [3] This results in a state of hypercontractility, or excessive contraction of the muscle fibers. [3]

Hypercontractility causes a high degree of mechanical stress on the muscle fibers, which may result in rupture or damage. [3] The current theory is that this damage is the underlying cause of nonexertional rhabdomyolysis associated with MYHM in horses. [3]

Mad About Horses
Join Dr. Chris Mortensen, PhD on an exciting adventure into the story of the horse and learn how we can make the world a better place for all equines.
Apple Podcasts Spotify Youtube
Mad Barn - Equine Nutrition Consultants

Risk Factors

IMM is most common in Quarter horses, Paint horses, Appaloosas, and other related stock horse breeds. [1] It is estimated that 7% of Quarter horses have the MYH1 mutation, with a higher prevalence in reining, working cow, and halter bred horses. [1][5]

Horses inherit the MYH1 genetic mutation from their parents. [1] Any horse carrying a single copy of the MYH1 mutation can develop symptoms of IMM. [1] Horses that have two copies of the MYH1 mutation, one from each parent, often have more severe symptoms and repeated episodes of IMM disorders. [1][6]

Symptoms

Symptoms of IMM often arise rapidly. [1] The main symptom of IMM is muscle wasting (atrophy). [1] Up to 40% of the horse’s muscle mass can atrophy within a 48-hour period once symptoms begin. [7]

Horses carrying two copies of the mutated MYH1 gene are more likely to experience symptoms, and often have more severe symptoms than horses with one copy of the mutation. [6] Around 40% of horses with a single copy of the mutation are symptom free. [6]

Less severely affected horses may display vague symptoms such as: [6]

These horses may require a more extensive diagnostic work-up to identify the cause of these symptoms.

Signs of Nonexertional Rhabdomyolysis

Some horses with IMM can also display symptoms of nonexertional rhabdomyolysis. Furthermore, the development of IMM can be triggered by a nonexertional rhabdoymyolysis episode. [1]

Symptoms of nonexertional rhabdomyolysis include: [1]

  • Muscle pain
  • Stiffness
  • Firm muscles
  • Weakness
  • Inability to rise from laying down (recumbency)
  • Red (bloody) urine
  • Muscle tremors

Diagnosis

Diagnosis of a muscle disorder is usually suggested based on the horse’s symptoms. Blood work can confirm muscle damage is occurring by showing elevation of muscle-associated proteins. [1]

Further investigation is necessary to identify the cause of muscle damage and to direct appropriate treatment and management. [1] Other muscle disorders that can cause similar symptoms to IMM include: [8]

Issues unrelated to the muscle itself, such as malnutrition or pituitary pars intermedia dysfunction (PPID) can also result in muscle atrophy. [8]

As the list of potential causes is long, an extensive work-up may be necessary to pinpoint the underlying muscle disorder. Diagnostics may include: [8]

  • Vitamin E level testing
  • Genetic testing
  • Muscle biopsy

Definitive diagnosis of IMM requires either a muscle biopsy showing signs of inflammation within the muscle, or genetic testing to identify the mutation. [1]

Muscle Biopsy

Veterinarians gather muscle biopsies from the affected muscles using a special biopsy punch or by removing a section of tissue surgically. [9] Many veterinarians biopsy the sacrocaudalis dorsalis medialis muscle which runs alongside the horse’s tailhead. [8]

To prepare for a biopsy, the veterinarian clips the biopsy site and prepares it with a surgical scrub to reduce the risk of infection. [9] They inject a local anesthetic such as lidocaine under the skin to numb the area completely. [9]

Depending on the technique for collecting the biopsy, the veterinarian may make an incision in the skin to gain access to the muscle. [9] Biopsy punches can be used through the skin, and do not require an initial incision. [9]

Once the biopsy sample is in hand, the veterinarian closes the site using sutures or skin staples. [9] Most horses heal from biopsy without complications. [9]

Genetic Testing

A genetic test for the myosin heavy chain myopathies is available. [10] To submit a sample for testing, 20 – 30 hairs from the horse’s mane are plucked for analysis. [10] These hairs must be pulled firmly from the mane to ensure that the hair bulbs, the part of the hair containing DNA, is present. [10]

Treatment

There is no definitive treatment for IMM in horses. [1] Although the initial episode of IMM may resolve, some horses develop recurring episodes of symptoms throughout their lives. [1] Treatment focuses on reducing symptoms when episodes occur. [1]

Immune-mediated myositis episodes result in massive muscle atrophy over a short time. [1] Treatment aims to slow or stop the progression of muscle atrophy to minimize muscle loss and allow the horse to begin regenerating lost tissue. [1]

Since the muscle atrophy results from an immune system attack on muscle fibers, a high dose of corticosteroids is used to control the immune system’s activity. [1] Corticosteroids also have an anti-inflammatory and pain control effect which helps improve comfort for the horse. [1]

Horses may require corticosteroid treatment for one month or longer, as it can take considerable time for the immune system to stop attacking the muscle fibers. [1]

Nonexertional Rhabdomyolysis Treatment

Horses with IMM can also experience episodes of nonexertional rhabdomyolysis, either in conjuction with or independent of IMM. Nonexertional rhabdomyolysis episodes are extremely painful, so treatment focuses on reducing pain and muscle stiffness. [1] Most episodes resolve within 24 hours with appropriate treatment. [1]

Many horses experiencing a rhabdomyolysis episode have high stress levels due to the sudden onset of pain and muscle tightness. [1] Many veterinarians sedate affected horses to reduce their anxiety and make them easier to handle. [1]

Treating the muscle pain and stiffness involves a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants. [1] Commonly used NSAIDs include phenylbutazone, flunixin meglumine, or ketoprofen. [1] Methocarbomol is the primary muscle relaxant available for horses, however its efficacy is variable. [1]

Once the horse’s symptoms stabilize and they are no longer in pain, treatment with dantrolene, another type of muscle relaxant, can prevent recurrence of future episodes during the recovery period. [1] This medication is usually given every hour until the horse’s blood work shows no signs of ongoing muscle damage. [1]

Most veterinarians also recommend treating for immune-mediated myositis after the horse recovers from the rhabdomyolysis episode, as rhabdomyolysis may trigger IMM. [1]

Prognosis

With appropriate treatment, the muscle damage from IMM can resolve over time. [1] Muscle regeneration can take weeks to months, and some horses may never fully recover. [1][11] Horses with two copies of the MYH1 mutation are less likely to fully recover. [6]

Around 50% of horses with IMM have recurring episodes. [6] These often occur within six months of the original episode. [11]

Performance

IMM may prevent affected horses from having successful performance careers. [1][6] One study showed that only 4 out of the 10 examined horses with two copies of the MYH1 mutation were competing successfully. [6]

Horses with one copy of the mutation have a higher chance of successful performance careers, with 71% of horses meeting their owners’ expectations in one study. [6]

Long-Term Management

Horses with IMM require ongoing management to prevent future episodes of muscle damage. [1]

These horses should not receive the strangles vaccine, and any other vaccinations should be given separately with a one-month gap between vaccines. [1] Intramuscular injections should also be avoided whenever possible. [1]

Owners must also take additional precautions to avoid exposure to infectious diseases, as these may trigger an IMM event. [1]

Prevention

The most effective means of prevention is avoiding breeding carriers of IMM, since horses with one copy of the mutation can develop symptoms. [1] Currently, genetic testing prior to breeding is recommended but not required in many breeds, including the Quarter horse. [1]

If a carrier of IMM is bred, they should be bred only to horses who do not carry the mutation. Breeding a carrier with one copy of MYH1 to a horse without the mutation has a 50% chance of producing a horse that carries the mutation. [1] Breeding two horses who each carry a single copy of the MYH1 mutation results in a 75% chance of producing another carrier. [1]

Summary

Immune-mediated myositis is a genetic disorder affecting the fast-twitch muscle fibers in horses.

  • IMM is one of two diseases under the myosin heavy chain myopathies (MYHM) umbrella that affect horses.
  • IMM occurs in response to a triggering event, with affected horses showing symptoms such as severe muscle atrophy and stiffness.
  • Diagnosis requires either a muscle biopsy or a genetic test.
  • IMM is not treatable, but episodes are manageable with medication.
  • IMM is preventable through genetic testing prior to breeding horses.

Is Your Horse's Diet Missing Anything?

Identify gaps in your horse's nutrition program to optimize their well-being.

References

  1. Valberg, S. J. Genetics of Equine Muscle Disease. Veterinary Clinics of North America: Equine Practice. 2020. doi: 10.1016/j.cveq.2020.03.012. View Summary
  2. Hyytiäinen, H. K. et al. Muscle Fibre Type Distribution of the Thoracolumbar and Hindlimb Regions of Horses: Relating Fibre Type and Functional Role. 2014. View Summary
  3. Ochala, J. et al. Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, MYH1E321G. Cells. 2021. doi: 10.3390/cells10123428. View Summary
  4. Finno, C. J. et al. A Missense Mutation in MYH1 Is Associated with Susceptibility to Immune-Mediated Myositis in Quarter Horses. Skeletal Muscle. 2018. doi: 10.1186/s13395-018-0155-0. View Summary
  5. Gianino, G. M. et al. Prevalence of the E321G MYH1 Variant for Immune‐mediated Myositis and Nonexertional Rhabdomyolysis in Performance Subgroups of American Quarter Horses. Veterinary Internal Medicine. 2019. doi: 10.1111/jvim.15393. View Summary
  6. Valberg, S. J. et al. Prevalence of Clinical Signs and Factors Impacting Expression of Myosin Heavy Chain Myopathy in Quarter Horse-Related Breeds with the MYH1E321G Mutation. Journal of Veterinary Internal Medicine. 2022. doi: 10.1111/jvim.16417. View Summary
  7. Lewis, S. S. et al. Suspected Immune-Mediated Myositis in Horses. Journal of Veterinary Internal Medicine. 2007. doi: 10.1111/j.1939-1676.2007.tb02996.x. View Summary
  8. Valberg, S. J. Muscle Conditions Affecting Sport Horses. Veterinary Clinics of North America: Equine Practice. 2018. doi: 10.1016/j.cveq.2018.04.004. View Summary
  9. Reed, S. M. et al. Equine Internal Medicine, 3rd ed. St. Louis, Mo: Saunders Elsevier, 2010.
  10. Equine Genetic Testing Veterinary Genetics Laboratory, University of California Davis. Accessed Dec. 12, 2023.
  11. Hunyadi, L. et al. Clinical Implications and Hospital Outcome of Immune‐Mediated Myositis in Horses. Veterinary Internal Medicine. 2017. doi: 10.1111/jvim.14637. View Summary