JPC SYSTEMIC PATHOLOGY
MUSCULOSKELETAL SYSTEM
March 2025
M-B01
Signalment (ACVP# 75-28): 5-month-old Hereford calf
HISTORY: This animal was from a feedlot containing 42 cattle. Over a period of 2 weeks, 4 calves died. The gross lesions consisted of hemorrhagic edematous foci in the muscles with gaseous crepitation of the adjacent tissues.
HISTOPATHOLOGIC DESCRIPTION: Skeletal muscle: Affecting 80% of the section, there is marked expansion of muscle fascia (epimysium, perimysium, and endomysium) up to 300µm, separating muscle fascicles and individual myocytes, by moderate to abundant amounts of fibrin, hemorrhage, and edema, admixed with degenerate neutrophils and karyorrhectic and cellular debris (necrosis). There is extensive acute, monophasic myofiber necrosis characterized by hypereosinophilic, fragmented sarcoplasm with loss of cross striations, nuclear pyknosis, and karyolysis. Less frequently, there are multifocal areas of myofiber degeneration characterized by myofiber swelling and vacuolation. Multifocally there are ectatic lymphatics and variably sized, up to 2mm diameter, well-demarcated clear spaces that compress adjacent myocytes (emphysema). Within adjacent adipose tissue, there is expansion by a neutrophilic, serohemorrhagic infiltrate admixed with abundant 2-4µm basophilic extracellular bacilli and beaded eosinophilic material (fibrin).
MORPHOLOGIC DIAGNOSES: 1. Skeletal muscle: Myositis, necrohemorrhagic, acute, diffuse, severe, with emphysema, edema, and numerous extracellular bacilli, Hereford, bovine.
ETIOLOGIC DIAGNOSIS: Clostridial myositis
CAUSE: Clostridium chauvoei
CONDITION: Blackleg
SYNONYMS: Black-quarter, emphysematous gangrene
GENERAL DISCUSSION:
- Economically important disease of pastured ruminants that occurs in warm wet months (summer) and is most common in beef cattle 9-months to 2-years of age that are rapidly growing and on a high plane of nutrition; often affects several animals within a few days and approaches a 100% case-fatality rate
- Spore forming, gram-positive, anaerobic bacillus; spores ubiquitous in soil, highly resistant to environmental changes and disinfectants, and persist in the environment for many years
- Characterized by the activation of latent spores in the muscle; best prevented with vaccination
PATHOGENESIS:
- Spores ingested during grazing > pass through the intestinal mucosal barrier > enter the bloodstream > spores disseminate to tissues, especially striated muscle and liver, and are dormant > spores germinate and multiply in low oxygen tension environments (e.g. trauma, hemorrhage, degeneration, necrosis) > toxin production > capillary damage, hemorrhage, edema > local severe necrotizing myositis and systemic toxemia
- Lecithinases and phospholipases punch holes in cell membranes of skeletal muscle and cause lysis of myocytes and endothelial cells
- Exotoxins include:
· Alpha toxin: Oxygen-stable hemolysin; necrotizing and hemolytic
· Beta: DNAse; hydrolyzes phosphodiester bonds in DNA
· Delta: Oxygen-labile hemolysin; forms pores in lysosomal membranes
· Gamma: Hyaluronidase; hydrolyzes hyaluronate linkages
· Neuraminidase: Removes sialic acids from glycoconjugates
TYPICAL CLINICAL FINDINGS:
- Frequently, animals are found dead without any observed clinical signs
- Typical initial signs are severe lameness, depression, anorexia, rumen stasis, fever (106oF), tachycardia (100-120 bpm), and elevated CK and AST
- Occasionally subcutaneous crepitation (emphysema) over the thigh, rump, loin, or shoulder
- Signs progress rapidly and include tremors, dyspnea (pulmonary edema), and death (circulatory collapse) in 12-36 hours; there is often a characteristic stiff extension of the affected limbs shortly after death
TYPICAL GROSS FINDINGS:
- Gross lesions vary with the age of the lesion; in earlier lesions muscles are dark red to red-black and moist at the periphery, are distended by serous/serohemorrhagic exudate, and are wet on cut surface; later lesions muscles are red-black, dry, friable, porous, and emphysematous, with a characteristic rancid butter odor (from butyric acid)
- Especially the large skeletal muscles of the pectoral and pelvic areas
- May affect any striated muscle, including heart (blackleg myocarditis), diaphragm, and tongue
- Fibrinohemorrhagic pleuritis without pneumonia; emphysematous myocarditis and necrosis; rapid post-mortem autolysis of liver, kidney and endocrine glands
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Monophasic muscle necrosis
- Focally extensive areas of muscle fibers with coagulation necrosis and fragmentation; interstitial edema; hemorrhage; gas bubbles
- Gram-positive bacilli (Clostridium chauvoei) are only occasionally evident
- Clostridium septicum can proliferate rapidly after death and obscure C. chauvoei
ADDITIONAL DIAGNOSTIC TESTS:
- Fluorescent antibody test on tissue smears
- Culture: Gram positive (catalase negative); strict anaerobe
- One step PCR technique for wet tissue and cultures
- Peroxidase-antiperoxidase immunohistochemical technique to identify Clostridium chauvoei in formalin-fixed paraffin-embedded tissues
DIFFERENTIAL DIAGNOSIS:
Myopathy:
- Pseudoblackleg/stable blackleg (Clostridium septicum): Multiple areas of deep-seated myonecrosis and hemorrhage in widely separated muscles without a detectable wound; less severe than blackleg, only occasional small gas bubbles; bloody gelatinous exudate
- Malignant edema (gas gangrene): Ruminants, horses, and swine especially susceptible; carnivores rarely affected; caused by Clostridium septicum, Clostridium perfringens, Clostridium novyi, Clostridium sordelli and Clostridium chauvoei acting individually or in combination; serohemorrhagic myositis and cellulitis with large gaseous and/or edematous areas next to wounds; typically characterized as a cellulitis rather than myositis
- Black’s disease (big head, Clostridium novyi): In big head of sheep, penetrating wounds on head establish the initial anaerobic environment; in cattle and sheep, black disease is associated with fluke migration (Fasciola hepatica) in the liver
- White muscle disease (M-M11): Young animals; associated with vitamin E and/or selenium deficiency; chalky white striations, degeneration, and necrosis of cardiac and skeletal muscle
- Ionophore toxicity (monensin) (M-T01): Cardiac and skeletal muscle necrosis; multifocal monophasic necrosis with regeneration (skeletal muscle) or fibrosis (cardiac muscle)
- Plant toxicity (Cassia occidentalis, coffee weed) (M-T02): Pale areas within skeletal and cardiac muscle; multifocal areas of necrosis with little to no mineralization
- Eosinophilic myositis (M-M12): May be a hypersensitivity reaction to Sarcocystis infection; green discoloration of affected muscles because of many eosinophils; myofiber necrosis
- Trueperella (formerly Arcanobacterium) pyogenes: Abscesses in skeletal muscles, primarily of the hind limbs, leading to swelling and lameness; encapsulated intramuscular abscess; diffuse purulent cellulitis extending down tissue planes; thick yellow-green, foul smelling pus; myonecrosis and fibrosis
- Protozoal myopathy (Sarcocystis sp.) (M-P04): Common incidental finding in skeletal muscle and cardiac myofibers; no inflammatory response unless cysts rupture
Sudden death in cattle:
- Malignant edema (see discussion above under myopathy differential diagnosis)
- Anthrax (Bacillus anthracis) (H-B01): Black, tarry, unclotted blood from external body orifices, no subcutaneous crepitation; large numbers of typical organisms usually identifiable on blood smears
- Bacillary hemoglobinuria (Clostridium hemolyticum) (D-B17): Large focal area of necrosis in the liver along with evidence of hemoglobinuria
- Dicumarol poisoning: Ingestion of moldy sweet clover (Melilotus sp.), or moldy sweet vernal (Anthoxanthum odoratum) hay: Multiple fresh hematomas in the carcass with absence of gross or histologic evidence of necrosis
- Other causes of sudden death: Grain overload, lightning strike
COMPARATIVE PATHOLOGY:
Clostridium chauvoei in other species:
- Sheep: Occurs in all ages; often secondary to wounds from shearing, tail docking, castration, or dystocia; deep, localized muscle lesions with little edema or gaseous crepitation; less common than in cattle
- Horses: Pectoral edema, stiff gait, incoordination; not well characterized
- Ratites: Paralytic disease characterized by recumbency, muscular weakness, dyspnea, and death in ostriches, with isolation of Clostridium chauvoei from necrotic lesions in the liver and areas of intestinal hemorrhage
- Deer: Outbreaks of the disease have been reported
REFERENCES:
- Cooper BJ, Valentine BA. Muscle and Tendon. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:230-34.
- Gal A, Castillo-Alcala F. Cardiovascular System, Pericardial Cavity, and Lymphatic Vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:687.
- Howerth EW, Nemeth NM, Ryser-Degiorgis MP. Cervidae. In: In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018: 164-165.
- Jones MEB, Gasper DJ, Mitchell E. Bovidae, antilocapridae, giraffidae, tragulidae, hippopotamidae. In: In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018: 133.
- Morrell EL, Odriozola E, Dorsch MA, et al. A review of cardiac blackleg in cattle, and report of 2 cases without skeletal muscle involvement in Argentina. J Vet Diagn Invest. 2022;34(6):929-936.
- Oliveira Junior CA, Silva ROS, Lobato FCF, et al. Gas gangrene in mammals: a review. J Vet Diag Invest. 2020;32(2):175-183.Richter V, Roch FF, Knauss M, et al. Animal-related factors predicting fatal cases of blackleg and gas gangrene in cattle. Vet Rec. 2021;189(10):e558.
- Stanton JB, Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:234.
- Valentine BA. Skeletal Muscle. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1010, 1016, 1024-1025.
- Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1170.