JPC SYSTEMIC PATHOLOGY
MUSCULOSKELETAL SYSTEM
April 2022
M-V01 (NP)

Signalment (ACVP #75-31):  Age unspecified ewe

 

HISTORY:  This ewe was 1 of 30 animals that presented with fever, facial edema, purulent nasal exudate, profuse salivation, ulcers at the commissures of the mouth, and coronitis.  At necropsy there were ulcers along the edge of the lips but no lesions in the oral cavity.  The coronary bands were hyperemic with hemorrhagic areas.  Muscles of the extremities displayed longitudinal light tan and dark red streaking of muscle fibers.  Multifocally the subcutis contained gelatinous edema fluid.

 

HISTOPATHOLOGIC DESCRIPTION:  Skeletal muscle:  Multifocally and randomly, 70% of myocytes are characterized by one of the following: pale, swollen, vacuolated sarcoplasm (degeneration); fragmented, eosinophilic to amphophilic, hyalinized sarcoplasm with loss of cross striations and nuclear pyknosis or karyorrhexis (necrosis) with occasional mineralization; or rarely increased sarcoplasmic basophilia with rows of centralized nuclei and occasional mitotic figures (regeneration).  Multifocally separating, surrounding, and replacing degenerate and necrotic myofibers and expanding the perimysium and endomysium are macrophages, few lymphocytes, plasma cells, and neutrophils, scattered hemorrhage, fibrin, edema, and variable amounts of reactive fibroblasts and collagen (fibroplasia).  Multifocally, few blood vessels are lined by hypertrophied endothelial cells or have disrupted endothelium and vessel walls that are fragmented and replaced by scattered pyknotic or karyorrhectic debris, fibrin, and few infiltrating neutrophils (fibrinoid and necrotizing vasculitis).  Multifocally within interstitial connective tissue there are few ectatic lymphatics (edema).  Within one myocyte, there is a single, oval, 40 x 60 um cyst containing numerous, elongate, 3 x 10 um basophilic bradyzoites (Sarcocystis sp.; slide variability).

 

MORPHOLOGIC DIAGNOSIS:  Skeletal muscle:  Degeneration and necrosis, multifocal, moderate, with rare regeneration, multifocal fibrinoid vasculitis, hemorrhage, mild histiocytic myositis, and fibroplasia, breed not specified, ovine.

 

ETIOLOGIC DIAGNOSIS:  Orbiviral myositis

 

CAUSE:  Bluetongue virus (BTV; ovine orbivirus)

 

CONDITION:  Bluetongue

 

GENERAL DISCUSSION:

• Reoviridae family; Orbivirus genus; double-stranded RNA, non-enveloped, single capsid
• Non-contagious, infectious viral disease that causes thrombo-hemorrhagic fevers primarily in sheep, goats, and cattle
• Disease is most severe in sheep, milder signs in cattle and nondomestic ruminants
• Transmitted by Culicoides arthropods (midges, gnats, sandflies); transmission through other biting insects and mother-to-fetus transmission have been documented
• Twenty-four known serotypes; no cross-protection between serotypes; five serotypes in North America, four serotypes vectored by sonorensis (BTV-10, -11, -13, and -17) and one serotype vectored by C. insignis (BTV-2)
• New strains of BTV in Europe have led to devastating disease in sheep and cattle (particularly serotype 8); morbidity ranges between 50-75% in naive sheep flocks, with 20-50% mortality
• Abortions and various congenital defects reported in both sheep and cattle; immunotolerance and persistent infections occur with prenatal infection
• Significant mortality in North American deer, bighorn sheep, and pronghorn antelope, but not in elk
  • White-tailed deer are highly susceptible and develop DIC and hemorrhagic diathesis; abortion and mummification have been reported
• Reservoir in wild ruminants; cattle and goats (usually asymptomatic)

 

PATHOGENESIS:

• Insect bite > peripheral circulation > primary replication in lymph nodes and spleen within conventional dendritic cells (cDCs), monocytes/macrophages, and endothelial cells with greater susceptibility reported in endothelial cells of lung micro-vascular system > viremia (leukocytes; erythrocytes) > secondary infection (vasculitis) of endothelial cells of arterioles, venules and capillaries > endothelial damage initiates local microvascular thrombosis and increased permeability leading to edema, hemorrhage, and ischemic necrosis (infarcts)
• Segmental necrosis of myofibers, satellite cells, and stromal cells > loss of satellite cells > decreased regeneration > fibrosis and scar formation
• BTV enters insect cells via viral inner core VP7 protein; enters mammalian cells via external capsid VP2 and VP5 hemagglutinin
• Several BTV serotypes stimulated expression of CD80 and CD86 costimulatory molecules on cDCs as well as cytokines involved in inflammation and immunity, i.e. IL12, IL1-β, and IL-6

 

TYPICAL CLINICAL FINDINGS:

Sheep:

• Pyrexia, cyanosis, dyspnea, nasal discharge, ptyalism, hyperemia and edema of eyelids and conjunctiva, coronitis, laminitis, lameness
• Bloody diarrhea, anorexia with rapid weight loss

Cattle and goats:

• Typically mild, often subtle disease; however, recent European BTV serotype 8 epizootic has been associated with clinical disease similar to BTV in sheep
• Calves from BTV-infected cows have been born with various congenital defects such as excessive gingival tissue, enlarged tongues, anomalous maxillae, and arthrogryposis

 

TYPICAL GROSS FINDINGS:

Sheep:

• Cyanosis of the buccal mucosa and tongue; oral erosions and ulcerations
• Ulceration of esophagus, rumen
• Pneumonia with enlarged, heavy, mottled lungs
• Edema of the subcutaneous and muscular tissue (lips, tongue, throat, brisket)
• Coronitis and laminitis; muscle infarction
• Abortion
• Hemorrhage at the base of the pulmonary artery (within tunica media) and within ruminal papillae
• Fetal infection during the first trimester (weeks 4-8) interferes with CNS organogenesis, resulting in hydrancephaly, porencephaly, retinal dysplasia, and arthrogryposis

Cattle and goats (European BTV serotype 8 epizootic):

• Ulceration of muzzle, oral mucosa, and teats
• Rhinitis and mucohemorrhagic nasal discharge
• Epiphora and periocular inflammation
• Limb edema
• Rarely, severely affected cattle develop pulmonary edema
• Neonatal calves have similar findings as neonatal sheep
• Transient corneal edema and blindness (calves)
• May develop thoracic, pericardial, and pulmonary effusions, myocardial hemorrhages and/or myocarditis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Vessels: Vasculitis with thrombosis, edema, and hemorrhage
• Left ventricular papillary muscles: Myofiber necrosis (infarcts)
• Skin and squamous mucosa: Vacuolation and necrosis of epithelial cells
• Skeletal muscle: Degeneration, necrosis, and regeneration with hemorrhage
• Hemorrhage at the base of the pulmonary artery within the tunica media
• Lungs: Pneumonia; alveolar septal congestion and edema
• Cerebrum: necrotizing encephalitis

 

ADDITIONAL DIAGNOSTIC TESTS:

• Serum neutralization; ELISA; AGID; fluorescent antibody; complement fixation
• Avidin-biotin complex immunoperoxidase method
• Reverse transcriptase PCR assay

 

DIFFERENTIAL DIAGNOSIS:

Muscle degeneration/necrosis:

• Clostridium chauvoei: “Blackleg”; myofiber necrosis with gas bubbles
• Clostridium septicum, Clostridium novyi: Gas gangrene
• Foot and mouth disease (FMD); aphthovirus, Picornaviridae: Myocardial necrosis
• Exertional rhabdomyolysis (capture myopathy)
• Monensin or other toxicities: Mineralization is usually less marked
• Nutritional myopathy: Vitamin E/selenium deficiency
• Physical injury

Similar systemic lesions:

Sheep:

• Foot and mouth disease (aphthovirus, Picornaviridae): Mild disease in sheep; vesicles in the mouth, muzzle, interdigital space, and teats
• Peste des petits ruminants (morbillivirus, Paramyxoviridae): Diphtheritic plaques and ulcers; intranuclear and intracytoplasmic inclusions, and syncytia
• Contagious ecthyma (parapoxvirus, Poxviridae): Vesicles, pustules, crusting of skin of the lips, nostrils, and eyes; often distinctly proliferative; may see eosinophilic ICIB
• Sheep pox (capripox virus): ICIB within epithelial cells, monocytes, and fibroblasts
• Photosensitization

Cattle:

• Foot and mouth disease (aphthovirus, Picornaviridae): Vesicles in the mouth, muzzle, interdigital space, and teats
• Vesicular stomatitis (vesiculovirus, Rhabdoviridae): Similar to foot and mouth disease
• Bovine virus diarrhea (pestivirus, Flaviviridae)
• Rinderpest (morbillivirus, Paramyxoviridae): Intranuclear and intracytoplasmic inclusions and syncytia
• Malignant catarrhal fever (ovine herpesvirus- 2 and alcelaphine herpesvirus 1, Gammaherpesviridae): Lymphoproliferative and necrotizing vasculitis and perivasculitis with characteristic lymphoblasts
• Photosensitization

 

COMPARATIVE PATHOLOGY (Orbiviruses):

Bluetongue Virus in other Species:  

• Highly susceptible: Sheep, white-tailed deer, mule deer, bighorn sheep, pronghorn antelope
• Mild to inapparent disease: Cattle (except in utero infections and BTV serotype 8 in Europe), goats, and elk; reported in South American camelids
• Serotype 8 has been reported in captive Eurasian lynx (being fed aborted fetuses of ruminants)
  • Subcutaneous hematomas, petechial hemorrhages, pulmonary congestion, and death
• BALB/c mice: neonatal mice were experimentally infected with Bluetongue virus exhibited severe necrotizing encephalitis and swelling and proliferation of endothelial cells

Other orbiviruses:

• Epizootic Hemorrhagic Disease (EHD) Virus:

• Affects white-tailed deer, black-tailed deer, pronghorn antelope, and elk; does not cause disease in sheep; reports in the US of EHD in cattle are increasing
• Acute, fulminant hemorrhagic disease in white-tailed deer (endemic in US)

• Differential diagnosis in deer: Atadenovirus (Odocoileus adenovirus 1) caused hemorrhagic disease outbreak in mule deer in California in 1990s and in other locations in U.S. since
• Two manifestations: (1) systemic (pulmonary edema and/or gastrointestinal hemorrhage) and (2) localized (upper intestinal)
• Cause endothelial cell hyperplasia and necrosis resulting in DIC
• Targets endothelium of larger vessels (in contrast to blue tongue and EHD which generally target microvasculature)
• Characteristic adenovirus INIB in endothelium
• Ibaraki disease: Found in Japan; a variant of EHD; produces a clinical disease similar to bluetongue in cattle, but does not affect sheep
• African horse sickness (equine orbivirus): Attacks endothelium, causing edema, especially around the eyes, nuchal ligament, pericardium

 

REFERENCES:

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