Musculoskeletal: clostridial myositis in Horses (Equis) | Vetlexicon
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Musculoskeletal: clostridial myositis

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Synonym(s): Clostridial myonecrosis, cellulitis, malignant edema

Introduction

  • A rapidly progressive condition involving liquefactive necrosis of muscle or other soft tissue, gas formation and clinical signs of toxemia.
  • Most affected horses have a history of recent intramuscular injection.
  • Cause: the disease is most commonly caused byClostridium perfringens  Clostridium perfringens  , but other clostridia may be isolated   Clostridia spp  .
  • The condition is peracute and is associated with a high mortality rate unless rapid and aggressive treatment is instituted.
  • Signs: subcutaneous emphysema, crepitation, lameness, tachycardia.
  • Diagnosis: hematology.
  • Treatment: penicillin, metronidazole, NSAIDs, surgical debridement, wound care/nursing.
  • Prognosis: high mortality rate.

Presenting signs

  • Diffuse, rapidly spreading areas of subcutaneous emphysema and crepitation.
  • Lameness, stiffness, tachycardia, increased digital pulse amplitude.

Acute presentation

  • Diffuse, rapidly spreading areas of subcutaneous emphysema and crepitation associated with intense pain.
  • The condition is peracute in onset and rapidly fatal if untreated.

Geographic incidence

  • Probably worldwide, although most cases have been reported from North America.

Age predisposition

  • In a retrospective series of 37 cases the median age at presentation was 3 years, with a range of 6 months to 20 years.

Breed/Species predisposition

  • None reported.

Public health considerations

  • The disease also occurs in humans, but is not a zoonosis.

Cost considerations

  • Treatment is intensive and aggressive, and will therefore be costly.

Pathogenesis

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

General
  • 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.

Diagnosis

Presenting problems

  • Diffuse, rapidly spreading areas of subcutaneous emphysema and crepitation.
  • Intense pain.

Client history

  • A history of recent intramuscular or inadvertent perivascular injection in most cases.
  • Some cases follow a laceration or occur at the site of a recent wound or surgical intervention.
  • Many horses are presented for apparent colic or rhabdomyolysis   Muscle: myopathy - exertional rhabdomyolysis  because of the severe pain associated with the cellulitis.

Clinical signs

  • Diffuse, rapidly spreading areas of subcutaneous emphysema and crepitation, associated with pyrexia.
  • Lameness, reluctance to move, stiffness, increased digital pulse amplitude, tachycardia.
  • The condition is peracute in onset and rapidly fatal if untreated.
  • The skin over the affected area is extremely cold to the touch.

Diagnostic investigation

  • Hematologic findings are variable   Blood: overview  : some horses show parameters within the reference range. Hemolytic anemia, thrombocytopenia and leukopenia may be present initially due to destruction by clostridial toxins. Alternatively, leukocytosis may also be present secondary to the severe inflammatory resopnse.
  • Most cases show increased levels of the muscle enzymes aspartate aminotransferase   Blood: biochemistry - aspartate amino transferase (AST)   and creatine kinase   Blood: biochemistry - creatine kinase  .
  • Evidence of multiple organ dysfunction, such as elevated renal or liver enzymes, may be seen.

Confirmation of diagnosis

Discriminatory diagnostic features

  • Presence of Gram-positive rods in aspirate of the area of soft tissue swelling.
  • Demonstration of gas shadows on ultrasound or radiography of the affected area.

Definitive diagnostic features

  • Culture ofClostridiumspp from an area of cellulitis or a wound.
  • Identification ofClostridiumspp by fluorescent antibody testing on appropriate tissue samples.

Gross autopsy findings

  • Severe necrotizing myositis and fasciitis in the area of the inciting wound or injection.
  • Some horses show evidence of multi-organ failure, with necrotic lesions in myocardium, spleen, kidneys and liver.
  • Severe necrotizing enterocolitis may also be observed.
  • Terminal disseminated intravascular coagulation may be indicated by petechial hemorrhages.

Histopathology findings

  • Severe necrotizing myositis and fasciitis, together with necrotic changes in other organs in some cases.

Differential diagnosis

Treatment

Initial symptomatic treatment

  • High dose crystalline penicillin (22,000-132,000 IU/kg IV every 4 h) together with metronidazole   Metronidazole   10-20 mg/kg PO QID.
  • Polyionic fluids.
  • Intravenous non-steroidal anti-inflammatories   Therapeutics: anti-inflammatory drugs  .
  • Steroids.
  • Equine plasma.

Standard treatment

  • High dose crystalline penicillin (22,000-132,000 IU/kg IV every 4 h).
  • Most cases warrant surgical debridement, which may involve myotomy and/or fasciotomy to improve oxygenation. Some horses require multiple fasciotomies. Infiltration of the myotomy/fasciotomy site with potassium penicillin, in conjunction with systemic therapy, has been used successfully in some cases.
  • Wound care and nursing requirements are extensive, which leads to a long period of hospitalization. In one report, the median duration of hospitalization was 12 days, with a range of 163 days. Hyperbaric oxygen therapy has been used for the treatment of similar conditions in man, and can be used in horses, if available.

Monitoring

  • Horses should be monitored for the development of respiratory distress due to either facial or pulmonary edema.
  • Multi-organ system dysfunction may also occur, therefore monitoring of kidney and liver function should be performed.

Subsequent management

Treatment

  • It has been reported that some horses may develop secondary immune-mediated hemolytic anemia and thrombocytopenia several days after initiation of penicillin treatment, necessitating a change in antibiotic. This should be differentiated from a cytotoxic anemia and thrombocytopenia by the timecourse of the development of hematologic changes.

Monitoring

  • Nasotracheal intubation or tracheotomy may be necessary if severe facial edema develops.
  • Significant scar tissue may develop at the site of the lesion.

Prevention

Control

  • Intramuscular injections should be given with care to induce minimal trauma and irritation.
  • This reduces the risk that a microenvironment that encourages germination of clostridial spores is created in devitalized skeletal muscle and other soft tissues.
  • Locally irritating substances, such as non-steroidal anti-inflammatory drugs and vitamin preparations should be given intravenously, if possible.
  • Giving drugs via deep intramuscular injection into highly vascularized tissues, such as the semimembranosis/semitendinosis muscles, may reduce, but not eradicate the risk.

Prophylaxis

  • There are no known injection site preparation techniques shown to be associated with the disease, making prophylaxis difficult.

Outcomes

Prognosis

  • Untreated cases are rapidly and almost invariably fatal.
  • The condition is generally associated with a high mortality rate (approximately 70%), although a recent retrospective study reported a mortality rate of only 27% (10/37 cases) in horses treated aggressively with both medical and surgical therapy at two US university teaching hospitals.
  • Performing surgical debridement within 24 h of hospitalization was associated with an improved survival rate (78%) over those that did not (40%).
  • Isolation ofC. perfringensas a single causative agent has been associated with a lower mortality rate (24%) than that associated with other clostridia in one study.
  • Isolation ofC. septicumor dual infection with two clostridial species were associated with a higher mortality rate (50%) in the same study.

Expected response to treatment

  • Treatment must be rapidly instituted, but with appropriate treatment the survival rate may be higher than previously reported.
  • The chance of survival may be improved with surgical debridement to improve oxygenation of the site.

Reasons for treatment failure

  • Failure to institute therapy rapidly.
  • Insufficiently aggressive antibiotic therapy and surgical debridement.
  • Infection with clostridia other thanC. perfringens, or mixed infection.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Flores-Díaz M & Alape-Girón A (2003) Role of Clostridium perfringens phospholipase C in the pathogenesis of gas gangrene. Toxicon 42 (8), 979-986 PubMed.
  • Weiss D J & Moritz A (2003) Equine immune-mediated hemolytic anemia associated with Clostridium perfringens infection. Vet Clin Pathol 32 (1), 22-26 PubMed.
  • Stevens D L & Bryant A E (1993) Role of theta toxin, a sulphydryl-activated cytolysin, in the pathogenesis of clostridial gas gangrene. Clin Infect DisSuppl 4, S195-S199 PubMed.
  • Brown C M, Kaneene J B & Walker R D (1988) Intramuscular injection techniques and the development of clostridial myositis or cellulitis in horses. JAVMA 193 (6), 668-670 PubMed.
  • Perdrizet J A, Callihan D R, Rebhun W C et al (1987) Successful management of malignant edema caused by Clostridium septicum in a horse. Cornell Vet 77 (4), 328-338 PubMed.
  • Rebhun W C, Shin S J, King J M et al (1985) Malignant edema in horses. JAVMA 187 (7), 732-736 PubMed.
  • Valberg S J & McKinnon A O (1984) Clostridial cellulitis in the horse: a report of five cases. Can Vet J 25 (2), 67-71 PubMed.
  • Bruehaus B A, Brown C M et al (1983) Clostridial muscle infections following intramuscular injections in the horse. J Eq Vet Sci 3, 42-46 VetMedResource.
  • Coloe P J, Ireland L & Vaudrey J C (1983) Clostridium fallax as a cause of gas-oedema in a horse. J Comp Path 93, 595-601 PubMed.
  • Reef V B (1983) Clostridium perfringens cellulitis and immune-mediated hemolytic anemia in a horse. JAVMA 182 (3), 251-254 PubMed.
  • Van Heerden J & Baths W S (1983) Clostridial myositisin a horse. J S Afr Med Assoc 53 (3), 211 PubMed.
  • Hagemoser W A, Hoffman L J & Lundvall R L (1980) Clostridium chauvoei infection in a horse. JAVMA 176 (7), 631-633 PubMed.

Other sources of information

  • Peek S F, Semrad S D & Perkins G D (2002) Clostridial myonecrosis in horses. In: Proc AAEP Conference 48, pp 131-133.
  • Vengust M, Arroyo L G, Weese J S, Staempfli H R & Baird J D (2002) Clostridial myositis: evaluation of normal equine skeletal muscle for the presence of clostridial spores. In: Proc AAEP Conference 48, pp 134-135.