Equine Exertional Rhabdomyolysis Study Guide

Overview and Clinical Importance

Exertional rhabdomyolysis (ER), commonly known as "tying-up," "azoturia," or "Monday morning disease," is a syndrome characterized by exercise-associated skeletal muscle damage resulting in muscle pain, stiffness, and reluctance to move. The term rhabdomyolysis literally means "dissolution of striated muscle." This condition has been recognized in horses for over 100 years and remains a significant performance-limiting or career-ending disorder for many equine athletes. ER represents a high-yield topic for the NAVLE due to its clinical significance, breed predispositions, and complex pathophysiology involving both sporadic and heritable forms.

The syndrome encompasses multiple distinct conditions with different underlying causes but similar clinical presentations. Understanding the classification, pathophysiology, diagnosis, and management of each form is essential for NAVLE success and clinical practice.

Classification of Exertional Rhabdomyolysis

Exertional rhabdomyolysis is broadly classified into two categories based on the underlying etiology:

Sporadic Exertional Rhabdomyolysis

Etiology and Risk Factors

Sporadic ER occurs when horses without intrinsic muscle defects experience muscle damage due to extrinsic factors. The most common causes include:

• Exercise exceeding conditioning level: Most common cause; occurs when training is accelerated too rapidly, especially after a rest period
• Electrolyte imbalances: Loss of sodium, potassium, calcium, and chloride through sweat during prolonged exercise in hot/humid conditions
• Viral respiratory infections: Exercise during active infection with EHV-1 or equine influenza increases risk
• Dietary imbalances: High grain intake combined with rest periods (classic "Monday morning disease")
• Vitamin E/Selenium deficiency: Can predispose to muscle damage, though not a primary cause

Polysaccharide Storage Myopathy Type 1 (PSSM1)

Pathophysiology

PSSM Type 1 is caused by a dominantly inherited mutation in the glycogen synthase 1 (GYS1) gene. This mutation (p.R309H - arginine to histidine substitution at position 309) results in a gain-of-function defect that causes constitutively active glycogen synthase enzyme. The consequences include:

• Excessive glycogen accumulation in skeletal muscle (1.8-fold higher than normal)
• Accumulation of abnormal amylase-resistant polysaccharide
• Enhanced insulin sensitivity leading to further glycogen storage
• Energy deficit during exercise despite abundant glycogen stores (glycogen is stored in non-bioavailable form)

Breed Predisposition and Prevalence

Clinical Signs

Clinical presentation varies by breed and severity:

Quarter Horse-related breeds: Episodes often begin at a young age with minimal exercise. Classic triggers include rest for a few days followed by return to work. Signs include tucked-up abdomen, camped-out stance, muscle fasciculations, sweating, gait asymmetry, and hindlimb stiffness.

Draft horses: May present with chronic progressive muscle wasting, weakness, and recumbency. Muscle enzymes may be normal between episodes. When rhabdomyolysis occurs, can be severe with marked CK/AST elevation and myoglobinuria.

Unique to PSSM1: Subclinical episodes with persistently elevated CK activity are common. CK remains elevated longer than in other forms of ER, even with rest.

Recurrent Exertional Rhabdomyolysis (RER)

Pathophysiology

RER is caused by abnormal intracellular calcium regulation in skeletal muscle. Unlike PSSM, horses with RER do NOT have abnormal glycogen storage. The proposed mechanism involves:

• Defective calcium release from the sarcoplasmic reticulum
• Enhanced sensitivity to stress hormones (catecholamines) causing excessive calcium release
• Muscle hypercontraction and subsequent necrosis
• Horses with RER show increased sensitivity to caffeine and halothane in vitro muscle contracture tests

Breed Predisposition and Risk Factors

Affected breeds: Thoroughbreds (5-10% develop RER during racing season), Standardbreds, and Arabians

Sex predisposition: Young fillies are overrepresented, suggesting hormonal influence

Temperament: Nervous, excitable horses are most commonly affected

Triggers: Stress, excitement, high-starch diet, stall confinement followed by exercise

Memory Aid - "RER = Racing, Excitement, Regulation": R - Racing breeds (Thoroughbreds, Standardbreds, Arabians), E - Excitement/stress triggers episodes, R - Regulation of calcium is abnormal. Remember: RER horses are typically "high-strung" fillies, while PSSM horses are typically calm, muscular horses!

Clinical Signs of Exertional Rhabdomyolysis

Clinical signs are similar across all forms of ER and typically occur during or shortly after exercise:

Diagnostic Approach

Serum Muscle Enzymes

Diagnostic Algorithm by Breed

Quarter Horses, Paints, Appaloosas, Draft breeds: Start with GYS1 genetic testing (blood or hair). If positive → PSSM1 diagnosis confirmed. If negative but clinical suspicion remains → muscle biopsy for PSSM2.

Thoroughbreds, Standardbreds, Arabians: GYS1 testing NOT recommended (mutation is rare/absent). Diagnosis of RER based on history, breed, repeated episodes, muscle biopsy showing centrally located nuclei without abnormal polysaccharide.

Warmbloods, Morgans, other breeds: Complete workup including GYS1 testing AND muscle biopsy, as both PSSM1 and PSSM2 occur.

Muscle Biopsy Findings

Treatment

Acute Episode Management

Immediate actions: Stop exercise immediately. Do NOT force the horse to move as this exacerbates muscle damage. Transport via trailer if distance is significant.

Long-Term Management

Dietary Management

Exercise Management

Memory Aid - "PSSM = Placid horses need Steady Movement": PSSM horses are typically calm and need daily exercise to burn glycogen. Avoid rest days! "RER = Reduce Excitement Regularly": RER horses are nervous and need stress reduction strategies. Keep them calm!

Prognosis

Sporadic ER: Excellent. Most horses recover within a few days with rest and supportive care. Episodes are unlikely to recur if underlying cause is addressed.

PSSM1: Good to guarded with appropriate management. Most horses can return to some level of performance with strict dietary and exercise protocols. Up to 90% of Quarter Horses show improvement with management.

RER: Variable. Interestingly, horses with RER that can race perform equally to unaffected horses. However, up to 15% of 2-3 year old Thoroughbreds with RER cannot train sufficiently to race at all. Many fillies are retired to broodmare careers.

Poor prognostic indicators: Recumbency, myoglobinuric renal failure, severe hyperthermia, and inability to rise are associated with guarded to poor prognosis.