Equine Myositis and Myopathy Study Guide

Overview and Clinical Importance

Equine myopathies and myositis represent a diverse group of muscle disorders that are frequently encountered in equine practice and constitute a significant portion of NAVLE examination content. These conditions range from acute exertional rhabdomyolysis ("tying up") to inherited metabolic disorders and toxic myopathies. Understanding the pathophysiology, clinical presentation, diagnosis, and management of these conditions is essential for veterinary practice.

The term rhabdomyolysis refers to the breakdown of skeletal muscle fibers with release of intracellular contents (myoglobin, creatine kinase, electrolytes) into the bloodstream. This can occur sporadically or as a chronic, recurrent condition with underlying genetic predisposition.

Classification of Equine Myopathies

Equine myopathies can be classified based on etiology and presentation:

Polysaccharide Storage Myopathy (PSSM)

Polysaccharide Storage Myopathy (PSSM) is one of the most common inherited muscle disorders in horses, characterized by abnormal glycogen accumulation in skeletal muscle fibers.

PSSM Type 1

Genetics: Autosomal dominant mutation in the glycogen synthase 1 (GYS1) gene. Affected horses have constitutively active glycogen synthase, resulting in 1.5-5 times higher muscle glycogen concentrations than normal horses.

Breed Predisposition: Quarter Horses (especially halter horses with approximately 28% prevalence), American Paint Horses, Appaloosas, Draft breeds (Belgian, Percheron), Morgans, and over 20 other breeds.

Clinical Signs: Muscle stiffness, pain, and reluctance to move typically occurring shortly after onset of exercise. Affected horses may display excessive sweating, firm and painful hindquarter muscles, a camped-out stance, and myoglobinuria (dark red-brown urine). Draft horses may show progressive weakness and muscle wasting rather than classic "tying up."

Diagnosis: Genetic testing (hair or blood sample) is the gold standard for PSSM1. Serum CK and AST are elevated during episodes. Muscle biopsy shows amylase-resistant, PAS-positive abnormal polysaccharide accumulation.

PSSM Type 2

Definition: PSSM2 refers to horses with abnormal glycogen accumulation in muscle biopsies but negative GYS1 genetic test. The exact cause remains unknown and may represent multiple distinct conditions.

Breed Predisposition: Warmbloods, Arabians, Morgans, Thoroughbreds, and some Quarter Horses. Many cases in Warmbloods have been reclassified as Myofibrillar Myopathy (MFM).

Clinical Signs: Often presents with poor performance, muscle soreness, stiffness, and gait abnormalities rather than classic tying up. Warmbloods may show reluctance to collect, engage hindquarters, or maintain a normal canter.

Diagnosis: Muscle biopsy is required (no validated genetic test available). Biopsy shows amylase-sensitive, PAS-positive glycogen accumulation, often subsarcolemmal in location.

PSSM Management

Recurrent Exertional Rhabdomyolysis (RER)

Recurrent Exertional Rhabdomyolysis (RER) is a chronic form of tying up caused by abnormal intracellular calcium regulation in muscle cells, leading to excessive muscle contraction.

Genetics: Suspected autosomal dominant inheritance in Thoroughbreds. The specific gene mutation has not been identified, but the condition appears familial.

Breed Predisposition: Thoroughbreds, Standardbreds, and Arabians. Fillies and mares are more commonly affected than males. Horses with nervous temperaments are at higher risk.

Triggers: Stress, excitement, nervousness, high-grain diets, irregular exercise schedules, and hormonal factors. Unlike PSSM, episodes often occur with light exercise rather than after prolonged work.

Clinical Signs: Muscle stiffness, pain, shortened stride, reluctance to move, sweating, elevated heart and respiratory rates, and myoglobinuria. Episodes may occur early in exercise, often associated with excitement or stress.

Diagnosis: History of multiple episodes with documented CK elevation, negative PSSM1 genetic test, and muscle biopsy showing increased central nuclei without abnormal polysaccharide. The gold standard is the caffeine-halothane contracture test (not widely available).

Management: Dietary NSC restriction to less than 20%, fat supplementation, consistent daily exercise, stress reduction, and in some cases dantrolene sodium prophylactically. Electrolyte supplementation may be beneficial for horses that sweat heavily.

Hyperkalemic Periodic Paralysis (HYPP)

Hyperkalemic Periodic Paralysis (HYPP) is an inherited muscle disorder caused by a defective skeletal muscle sodium channel, resulting in episodes of muscle tremors, weakness, or paralysis associated with elevated blood potassium levels.

Genetics: Autosomal dominant mutation (c.4248C>G) in the sodium channel gene SCN4A. All affected horses trace back to the Quarter Horse stallion "Impressive." Approximately 4.4% of Quarter Horses carry the mutation.

Breed Predisposition: Quarter Horses, American Paint Horses, Appaloosas, and Quarter Horse crossbreds. Most commonly seen in halter horses due to selective breeding for heavy muscling (a secondary effect of the mutation).

Pathophysiology: The mutated sodium channels fail to inactivate properly when potassium levels rise, causing persistent muscle fiber depolarization and involuntary contraction or weakness.

Clinical Signs: Episodes typically begin by 2-3 years of age. Signs include muscle fasciculations and tremors, third eyelid prolapse, weakness, stiff gait, inability to stand, respiratory stridor (upper airway muscle paralysis), and in severe cases collapse and sudden death from cardiac arrest or respiratory failure. Episodes last 15-60 minutes and occur sporadically, often triggered by stress, fasting, high-potassium diets, or anesthesia.

HYPP Triggers and Diagnosis

Common Triggers: High-potassium feeds (alfalfa hay, molasses, soybean meal, electrolyte supplements, brome hay), fasting followed by feeding, stress, transportation, general anesthesia, and concurrent illness.

Diagnosis: Genetic testing (hair or blood) is definitive. Results are reported as N/N (normal), N/H (heterozygous, affected), or H/H (homozygous, more severely affected). During episodes, serum potassium is elevated (greater than 5.5 mEq/L). Since 2007, AQHA does not register H/H foals.

HYPP Management

Malignant Hyperthermia (MH)

Malignant Hyperthermia (MH) is a rare, life-threatening inherited disorder triggered by certain anesthetics or stress, causing uncontrolled calcium release in muscle cells and a hyper-metabolic crisis.

Genetics: Autosomal dominant mutation (c.7360C>G) in the ryanodine receptor 1 (RYR1) gene. The defective calcium release channel causes excessive intracellular calcium accumulation when triggered.

Breed Predisposition: Quarter Horses and American Paint Horses. Affects less than 1% of the Quarter Horse population. Can occur concurrently with PSSM1 and/or HYPP, greatly exacerbating clinical signs.

Triggers: Halogenated anesthetics (halothane, isoflurane), succinylcholine, and occasionally stress, excitement, or exercise.

Clinical Signs: Rapidly developing muscle rigidity, tachycardia, tachypnea, profuse sweating, severe hyperthermia (body temperature can reach 113°F/45°C), metabolic acidosis, hyperkalemia, and cardiac arrhythmias. Episodes are often fatal (approximately 34% mortality).

Diagnosis: Genetic testing (hair or blood) before anesthesia is recommended for Quarter Horse-related breeds. Clinical diagnosis during episodes based on characteristic signs under anesthesia.

Treatment: Immediate discontinuation of triggering anesthetic, supportive care with IV fluids, external cooling, mechanical ventilation, and dantrolene sodium (4 mg/kg IV). Prophylactic dantrolene (4 mg/kg PO) 30-60 minutes before anesthesia in known carriers. Avoid inhalant anesthetics in positive horses.

Immune-Mediated Myositis (IMM) / Myosin Heavy Chain Myopathy (MYHM)

Myosin Heavy Chain Myopathy (MYHM) encompasses two clinical syndromes caused by a mutation in the MYH1 gene: Immune-Mediated Myositis (IMM) characterized by rapid muscle atrophy, and non-exertional rhabdomyolysis.

Genetics: Autosomal dominant mutation (E321G) in the MYH1 gene encoding fast-twitch type 2X myosin heavy chain. Variable penetrance means not all horses with the mutation develop disease. Prevalence is approximately 7% in general Quarter Horse population, higher in reining (24%) and halter (16%) horses.

Breed Predisposition: Quarter Horses and related breeds (Paint, Appaloosa). Bimodal age distribution: young horses less than 8 years or older horses greater than 16 years.

Triggers: Approximately 39% of cases have history of triggering factor: Streptococcus equi infection (strangles) or vaccination, respiratory viral infections (influenza, EHV), Pigeon fever, or vaccination with flu/rhino or strangles vaccines.

IMM Clinical Signs: Rapid, dramatic muscle atrophy (up to 40-50% muscle mass loss within 48-72 hours) predominantly affecting topline and gluteal muscles. Stiffness, malaise, and moderate CK elevation. Rarely progresses to systemic calcinosis (poor prognosis).

Non-exertional Rhabdomyolysis Clinical Signs: Severe muscle damage (high CK/AST) without prominent atrophy, not associated with exercise. More common in young Quarter Horses.

Diagnosis: Genetic testing for MYH1 mutation. Muscle biopsy of affected muscles shows lymphocytic infiltration of myofibers, vasculitis, necrosis, and regeneration.

Treatment: Antibiotics if concurrent infection, corticosteroids (dexamethasone 0.05 mg/kg IV daily for 3 days, then prednisolone 1 mg/kg PO daily tapered over 4-6 weeks). Muscle mass typically recovers over 2-3 months. Recurrence is common, especially in homozygotes.

Atypical Myopathy / Seasonal Pasture Myopathy

Atypical Myopathy (AM) in Europe and Seasonal Pasture Myopathy (SPM) in North America are highly fatal toxic myopathies caused by ingestion of hypoglycin A from specific maple tree species.

Etiology: Hypoglycin A is a natural toxin found in seeds (samaras) and seedlings of sycamore maple (Acer pseudoplatanus) in Europe and box elder (Acer negundo) in North America. The toxin is metabolized to methylenecyclopropyl acetic acid (MCPA), which inhibits mitochondrial fatty acid oxidation enzymes (acquired MADD).

Seasonality: Most cases occur in autumn (when seeds fall) and spring (when seedlings sprout). Risk factors include extended turnout (greater than 12 hours daily), sparse pasture with limited forage, proximity to affected maple trees, young horses, and negative energy balance.

Clinical Signs: Acute onset of weakness, muscle stiffness, reluctance to move, recumbency, hypothermia (not hyperthermia), tachycardia, tachypnea, congested mucous membranes, and characteristic dark red-brown urine (myoglobinuria). Horses may remain alert and willing to eat. Clinical signs appear within 12-72 hours of ingestion.

Diagnosis: Markedly elevated CK (often greater than 100,000 U/L), AST, and LDH. Serum acylcarnitine profile showing increased short and medium-chain acylcarnitines is diagnostic. Detection of hypoglycin A or MCPA in blood or urine confirms exposure. Myoglobinuria is common.

Prognosis: Very poor, with mortality rates of 75-90%. Death typically occurs within 2-3 days. Horses that remain standing have better prognosis than recumbent horses.

Treatment: Intensive supportive care: IV fluids for renal protection, glucose/dextrose to provide alternative energy substrate, B vitamins (riboflavin, L-carnitine), vitamin E supplementation, analgesia. No specific antidote exists.

Prevention: Remove horses from pastures with sycamore maple or box elder trees during high-risk seasons. Fence off trees, remove fallen seeds and seedlings, provide adequate forage supplementation, limit turnout duration. Field maple (A. campestre) and Norway maple (A. platanoides) do NOT contain hypoglycin A and are safe.

Nutritional Myodegeneration (White Muscle Disease)

Nutritional Myodegeneration (NMD), also known as White Muscle Disease, is a myodegenerative disease caused by dietary deficiency of selenium and/or vitamin E, primarily affecting foals born to deficient dams.

Etiology: Selenium and vitamin E are essential antioxidants that protect cell membranes from oxidative damage. Deficiency occurs in geographic regions with selenium-deficient soils (Pacific Northwest, Northeast, Great Lakes region of North America) or when horses are fed locally-sourced forage from these areas without supplementation.

Affected Animals: Most commonly young, rapidly growing foals (birth to several months of age) born to selenium-deficient dams. Adult horses can also be affected, particularly with masseter muscle involvement or vitamin E-responsive myopathy.

Clinical Forms: Peracute (cardiac) form presents with sudden death, dyspnea, and arrhythmias due to myocardial necrosis. Subacute (skeletal) form shows weakness, stiff gait, difficulty rising, muscle tremors, dysphagia (tongue and pharyngeal muscle involvement), and aspiration pneumonia.

Diagnosis: Elevated serum CK and AST. Whole blood selenium less than 0.07 mcg/mL (reference greater than 0.15 mcg/mL) and/or serum vitamin E less than 2 mcg/mL. Hyperkalemia, hyperphosphatemia, and hypocalcemia may occur with severe rhabdomyolysis.

Treatment: Injectable selenium (0.055-0.067 mg/kg IM once) with oral vitamin E supplementation (5000-10000 IU/day of natural vitamin E). Supportive care including fluids, nasogastric feeding if dysphagia present, and antibiotics for aspiration pneumonia.

Prevention: Selenium supplementation of pregnant mares (1-3 mg selenium daily for adult horse). Use of selenium-fortified feeds or ration balancers. Know the selenium status of your region and forage sources.

Prognosis: Good for skeletal form if treated early. Cardiac form is often fatal.

Diagnostic Approach to Equine Myopathy

Key Serum Biomarkers

Available Genetic Tests

Summary Comparison Table