November 2018



Signalment (JPC #1782714): 3-month old Hereford calf


HISTORY: This calf had a history of severe chronic diarrhea and oral erosions for a 1-week period prior to death.


MICROSCOPIC DESCRIPTION: Slide D-V21a: Rumen: Focally extensively, rumenal mucosal epithelium is thickened up to 2mm (hyperplastic) with acanthosis and markedly swollen squamous epithelial cells with abundant clear to light eosinophilic, flocculent, vacuolated cytoplasm (ballooning degeneration), and often contain a single, up to 20 um, eosinophilic, intracytoplasmic viral inclusion body. Multifocally, vacuolated cells coalesce to form clear spaces up to 100-200 um in diameter which often contain numerous viable and degenerate neutrophils admixed with fibrin, hemorrhage and necrotic debris (intraepithelial pustules) and scattered single cell necrosis. Multifocally epithelium is eroded, ulcerated and replaced by cellular and karyorrhectic debris, abundant viable and degenerate neutrophils, and scattered colonies of superficial cocci (serocellular crust), and the remaining hyperplastic epithelium contains moderate parakeratotic hyperkeratosis. The lamina propria and submucosa contains abundant degenerate neutrophils, fewer macrophages, lymphocytes and plasma cells, and hemorrhage, and blood vessels often contain plump endothelial cells (reactive). Collagen bundles within the lamina propria and submucosa and muscle bundles of the tunica muscularis are separated by increased clear space, with multifocal ectatic lymphatics (edema).


Tongue: Multifocally, myocytes within the tunica muscularis are mildly hypereosinophilic, with loss of cross-striations and pyknotic nuclei (degeneration and necrosis), with small cytoplasmic aggregates of a basophilic globular to granular material (mineralization).


Slide D-V21b: Esophagus: Affecting over 70% of the section, the mucosal epithelium is thickened up to 1 mm (hyperplastic), and there is extensive, severe intracellular edema (ballooning degeneration), with similar formation of intraepithelial pustules, and numerous previously described eosinophilic intracytoplasmic viral inclusion bodies. Focally, there is an extensive area of ulceration and replacement with moderate amounts of eosinophilic cellular and karyorrhectic debris, viable and degenerate neutrophils, hemorrhage, abundant fibrin, granulation tissue and many superficial cocci (serocellular crust). In the adjacent subepithelial connective tissue, there is diffuse mild congestion and many viable and degenerate neutrophils, fewer macrophages, lymphocytes, and plasma cells. Blood vessels often contain plump endothelial cells (reactive).


MORPHOLOGIC DIAGNOSIS: 1. Rumen: Rumenitis, proliferative and necrotizing, subacute, focally extensive, severe, with ballooning degeneration, hyperkeratosis, intraepithelial pustules and numerous epithelial eosinophilic intracytoplasmic viral inclusion bodies, Hereford, bovine.

2. Esophagus: Esophagitis, proliferative and necrotizing, subacute, diffuse, severe, with ballooning degeneration, intraepithelial pustules and numerous epithelial eosinophilic intracytoplasmic viral inclusion bodies.

3. Tongue, myocytes: Necrosis and mineralization, multifocal, minimal.


ETIOLOGIC DIAGNOSIS: Parapoxviral esophagitis and rumenitis


CAUSE: Bovine papular stomatitis virus (bovine parapoxvirus)


CONDITION: Bovine papular stomatitis; infectious ulcerative stomatitis and esophagitis



·      Mild papular and necrotizing disease of the oral cavity; occasionally the esophagus and forestomachs

·      Most common in young calves or immunosuppressed adults; frequently associated with deficient colostrum administration

·      Typically not a clinically significant infection; important to differentiate from other more serious diseases causing oral lesions (e.g. foot and mouth, vesicular stomatitis, etc.)

·      Zoonotic; causes papules located on fingers and arms of humans that may persist for several weeks

·      Chronic form is reported but less common



·      Virus shed in nasal secretions and saliva

·      Spread by direct contact with wounds or by fomites

·      Infective virus is located within the epithelial cells of lesions

·      Infection does not confer immunity; relapses can occur



·      Morbidity approaches 100% within a group, but signs are mild to inapparent

·      Occasionally, transient anorexia, weight loss, ptyalism, +/- slight fever

·      Most infections acute and resolve within approximately 1 week

·      Chronic form: Stomatitis



·      Lesions occur on the muzzle, anterior nares, inner aspect of the lips, gingiva, buccal papillae, dental pad, hard palate, ventral and lateral (not dorsal) surfaces of the tongue, and occasionally the esophagus and forestomachs

·      Most common lesion: Sharply demarcated erythematous round macule that develops rapidly into a raised papule, then undergoes central necrosis

·      These circular, coin-shaped lesions often have a hyperemic, thickened periphery

·      Lesions often coalesce

·      Lesions heal quickly (4-7 days) and leave a reddish brown area after regression

·      Vesicles are not present

·      Chronic form: Necrotizing and proliferative stomatitis



·      Epithelial hyperplasia up to two times normal depth, acantholysis, and ballooning degeneration in deeper levels

·      Congestion and edema in the lamina propria and submucosa, with low numbers of macrophages, lymphocytes and plasma cells

·      Dense eosinophilic intracytoplasmic inclusion bodies in vacuolated cytoplasm, especially in cells at active margin of lesions

·      Basilar epithelium unaffected

·      Chronic form: Parakeratotic hyperkeratosis, pseudoepitheliomatous hyperplasia, fewer intracytoplasmic inclusion bodies



·      Virions have a regular spiraled filamentous surface pattern (resembles ball of yarn or coil of rope) and are 320 x 125 nm

·      Slightly smaller and more ovoid than other poxviruses



·      Electron microscopy of the saliva

·      Virus isolation

·      Virus neutralization test; indirect immunofluorescence; PCR



Oral lesions in cattle

·      Foot-and-mouth disease (Picornaviridae, aphthovirus): Vesicles, mucosal sloughing, necrosis and ulceration

·      Vesicular stomatitis (Rhabdoviridae, vesiculovirus): Vesicles, mucosal sloughing, necrosis and ulceration

·      Bovine virus diarrhea/mucosal disease (Flaviviridae, pestivirus): Mucosal epithelial erosions, blunting of buccal papillae

·      Rinderpest (Paramyxoviridae, morbillivirus): Necrotizing foci and oral erosions; syncytia, intranuclear and intracytoplasmic inclusion bodies

·      Malignant catarrhal fever (alcelaphine herpesvirus 1 or ovine herpesvirus 2): Oral erosions, scabs on muzzle; fibrinoid vascular necrosis

·      Bluetongue (Reoviridae, orbivirus): Clinical disease rare in cattle; insect vector, seasonal

·      Infectious bovine rhinotracheitis (bovine herpesvirus type 1, alphaherpesvirus): Hyperemia of muzzle ("red nose"), pustules on nasal mucosa that later develop into plaques; eosinophilic intranuclear inclusions; outbreaks in newborn calves



Other Parapoxviruses

·      Orf virus: Causes contagious ecthyma in sheep and goats; orf in humans

·      Parapoxvirus of red deer in New Zealand: Genomically distinct parapoxvirus isolated from red deer in New Zealand

·      Pseudocowpox virus: Lesions usually confined to the udder and rarely the medial thighs or scrotum; usually no systemic signs of illness; causes “milker’s nodules” in humans

·      Parapoxviruses also isolated from harbor seals, northern fur seals, gray seals, northern elephant seals, South American sea lions, reindeer, chamois, muskoxen, camels, gazelles, wild Japanese sorrows, red and gray squirrels, pygmy chimpanzees

·      Humans: Parapoxviruses from multiple animal species produce erythematous papules on the hands, fingers or forearms



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8.    Smith BP. Bovine popular stomatitis (proliferative stomatitis). In: Smith BP, ed. Large Animal Internal Medicine. 5th ed. St. Louis, MO: Elsevier Mosby; 2015:750.

9.    Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:139-140.

10. Viral diseases of the ruminant alimentary tract. In: Constable PD, Hinchcliff KW, Done SH, Grunberg W, eds. Veterinary Medicine, A Textbook of the Diseases of Cattle, Horses, Sheep, Pigs, and Goats. 11th ed. St. Louis, MO: Elsevier; 2017:601-603.

11. Zachary JF. Mechanisms of microbial infections. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:202.

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