Etiology

• Clostridium perfringensis most commonly isolated   Clostridium perfringens  .
• Cases have also been associated withClostridium novyi,C. septicum,C. fallax,C. ramosum,C. tertium,C. sporogenesandC. chauvoei  Clostridia spp  .
• More than one species ofClostridiummay be isolated from an individual case.

Predisposing factors

• Most equine cases are associated with intramuscular injection. 
• It has been shown that dormant clostridial spores from various species, includingC. histolyticumandC. sporogenes, which have been associated with myonecrosis in humans, are present in skeletal muscle tissue of healthy horses.
• Injections associated with this syndrome have been made into the cervical muscles, gluteals, semimembranosis/semitendinosis muscles (hamstrings), or a combination of all.
• Perivascular leakage of an intravenous injection may also be a causative factor.
• Other cases occur following a wound, laceration or surgical intervention.

Specific

• Injection of various drugs has been linked to clostridial myositis by anecdotal evidence.
• Flunixin meglumine is the most commonly associated drug being cited as the causative agent in 50% of cases in one study.
• Other drugs that have been reported include vaccines, B vitamins, dipyrone, selenium, ivermectin, dextrose, flunixin meglumine, epinephrine, frusemide, antihistamines and dexamethasone.

Pathophysiology

• Histotoxic or tissue-destroying clostridia cause an exotoxin-mediated inflammatory cascade.
• It is thought that enteric clostridial organisms gain entry into the systemic circulation and may become embedded in skeletal muscle.
• High oxygen tension in muscle tissues may induce formation of dormant clostridial spores.
• Tissue inflammation may then be stimulated by a local or systemic insult, and provides an appropriate anaerobic microenvironment for germination of previously dormant clostridial spores.
• Phospholipase C (Cp-PLC) ofC. perfringens, also called alpha-toxin, is thought to be the major virulence factor involved in gas gangrene.
• This toxin increases capillary permeability, decreases cardiac contractility, induces platelet aggregation, hemolysis and myonecrosis, and is lethal in experimental animal models.
• The theta toxin ofC. perfringensis also thought to be involved in pathogenesis of the syndrome. The rapid tissue necrosis associated withC. perfringensinfection may be at least partly due to progressive vascular compromise induced by theta toxin. 
• In high concentrations theta toxin directly induces vascular injury at the site of infection. At lower concentrations it activates leukocytes and endothelial cells, and therefore provokes more distant vascular injury.

Timecourse

• Signs develop within 672 h of the predisposing tissue insult and progress rapidly.

Epidemiology

• The causative organisms are probably derived from the animals own intestinal flora.