JPC SYSTEMIC PATHOLOGY
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: Diffusely, muscle fibers are either swollen with vacuolated sarcoplasm (degeneration) or fragmented, with eosinophilic to amphophilic hyalinized sarcoplasm, loss of cross striations, pyknosis, and karyorrhexis (necrosis) with occasional mineralization. Multifocally, separating, surrounding, and replacing degenerate and necrotic myofibers are macrophages, few lymphocytes, plasma cells, and neutrophils, scattered hemorrhage and fibrin, and variable amounts of reactive fibroblasts and collagen (fibroplasia). There is rare regeneration characterized by invasion of lightly basophilic myofibers by satellite cells, forming a row of centralized nuclei, and occasional mitotic figures (myoblasts). Multifocally, few blood vessels are lined by hypertrophied endothelial cells or have a disrupted endothelium with vessel walls that are fragmented and replaced by scattered pyknotic or karyorrhectic debris, fibrin, and few infiltrating neutrophils (fibrinoid and necrotizing vasculitis). Between extant muscle fibers, there is increased clear space and 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.).
- Skeletal muscle: Degeneration and necrosis, multifocal, moderate, with regeneration, multifocal fibrinoid vasculitis, hemorrhage, histiocytic myositis, and fibrosis, breed not specified, ovine.
- Skeletal muscle, myocyte: Sarcocyst.
ETIOLOGIC DIAGNOSIS: Orbiviral myositis
CAUSE: Bluetongue virus (BTV; ovine orbivirus)
- Reoviridae family; Orbivirus genus; double-stranded RNA, non-enveloped, single capsid
- Non-contagious, infectious viral disease that causes thrombo-hemorrhagic fevers in sheep and other 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)
- 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 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:
- Pyrexia, cyanosis, dyspnea, nasal discharge, and ptyalism
- Hyperemia and edema of eyelids, 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:
- 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
- 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 (recent 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
- Transient corneal edema (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)
- Skeletal muscle: Degeneration and necrosis with hemorrhage
- Hemorrhage at the base of the pulmonary artery within the tunica media
- Lungs: Pneumonia; alveolar septal congestion and edema
ADDITIONAL DIAGNOSTIC TESTS:
- Serum neutralization; ELISA; AGID; fluorescent antibody; complement fixation
- Avidin-biotin complex immunoperoxidase method
- Reverse transcriptase PCR assay
- 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:
- 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 affecting lips, nostrils and eyes; often distinctly proliferative; may see eosinophilic ICIB
- Sheep pox (capripox virus): ICIB within epithelial cells, monocytes, and fibroblasts
- 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 admixed with characteristic lymphoblasts
White-tailed deer and mule deer:
- Epizootic hemorrhagic disease (adenovirus): Characteristic adenovirus INIB
- Mule deer: Odocoileus adenovirus-1 (Atadenovirus)
COMPARATIVE PATHOLOGY (Orbiviruses):
- Highly susceptible: Sheep, white-tailed deer, mule deer, bighorn sheep, pronghorn antelope are highly susceptible
- Mild to inapparent disease: Cattle (except in utero infections and BTV serotype 8 in Europe), goats and elk; reported in South American camelids
- Epizootic hemorrhagic disease (EHD): White-tailed deer, black-tailed deer, pronghorn antelope, and elk
- Acute, fulminant hemorrhagic disease in white-tailed deer (endemic in US)
- Does not cause disease in sheep
- Reports in the US of EHD in cattle are increasing
- Atadenovirus (Odocoileus adenovirus 1) as cause of 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)
- 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
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