Muscle / Sport

Question 1

What are the myopathies associated with Streptoccus equi equi infection ?

Answer 1

• Infarctive PH : serum CK activity is markedly elevated (>35,000 U/L) and horses are painful with firm swollen areas in pectoral, abdominal and crus muscles, muscles that are compressed when horses are lying down. Aggressive and prolonged corticosteroid treatment is essential in cases of infarctive PH to prevent fatal infarction of the gastrointestinal tract, lungs and other tissues.
• Myosin Heavy Chain Myopathy (MYHM) : Quarter Horse-related breeds are particularly susceptible to compli-
  cations from S. equi infection because of a genetic proclivity for myosin heavy chain myopathy (MYHM) caused by an E321G mutation in the myosin heavy chain 1 gene (MYH1) encoding type 2X myosin. In approximately 40% of cases of MYHM, a history of exposure to S. equi, other infectious diseases or vaccination with S. equi or influenza / rhinopneumonitis precedes clinical signs. Both horses heterozygous and homozygous for the MYH1 mutation develop MYHM with clinical signs being more severe and difficult to manage in homozygotes.
  Horses with MYHM may present with : immune-mediated myositis (IMM), calciphylaxis, nonexertional rhabdomyolysis (nER).
• IMM : Immune-mediated myositis usually develops in horses < 8 years of age or >16 years of age and is characterised by rapid profound atrophy of gluteal and epaxial muscle initially concurrent with moderate serum CK and AST elevations (often < 20,000 U/L). The aetiology of IMM has been proposed to be a loss of self-tolerance to type 2X myosin. The amino acid sequence of SEM overlaps that of type 2X myosin creating the possibility that antigenic mimicry is an instigator of disease.
  In the early phase of gluteal and epaxial muscle atrophy, lymphocytes infiltrate type 2X muscle fibres and cuff small blood vessels.
• Calciphylaxis : Systemic calcinosis or calciphylaxis is a rare sequelae to IMM in young (less than 9 years of age) horses with the MYH1 mutation. Severe atrophy is followed by diverse organ failure due to systemic dystrophic calcification.
  A high product of serum calcium multiplied by serum phosphorus (>65 mg/dL) is common in calciphylaxis.
• Nonexertional rhabdomyolysis : 67% of nER cases in Quarter Horse-related breeds were associated with the MYH1 mutation of which 75% were homozygotes and 25% heterozygotes. Severe, generalised muscle degeneration occurs with serum CK and AST in the hundreds of thousands. Triggering factors include infection with S. equi, Anaplasma phagocytophilum, Corynebacterium pseudotuberculosis and other infectious agents but often the trigger is unknown.
  Muscle biopsies of gluteal or epaxial muscles show acute muscle degeneration, glycogen depletion in large muscle fibres and, unlike IMM, < 18% of horses have lymphocytic infiltrates in muscle fibres. This suggests an alternate aetiology to immune-mediated muscle fibre destruction. The MYH1 mutation appears to enhance the calcium sensitivity of muscle fibres which could result in a hyper-contractile state where muscles are more likely to contract and fail to relax triggering myodegeneration.

Myopathies associated with Streptococcus equi equi infection
eve 2024