JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
November 2021
D-V17

 

Signalment (JPC #2317403):  A kudu

 

HISTORY:  This animal lived in Kruger National Park, South Africa.

 

HISTOPATHOLOGIC DESCRIPTION:  Tongue:  The stratum spinosum of the lingual mucosa is expanded by a 5x2mm, well-demarcated vesiculopustule that contains innumerable viable and necrotic neutrophils, occasional sloughed keratinocytes that are either swollen with vacuolated cytoplasm (degeneration) or shrunken and angular with hypereosinophilic cytoplasm and pyknotic to karyorrhectic nuclei (necrosis), abundant eosinophilic fluid, moderate amounts of beaded fibrillary materal (fibrin), and mild hemorrhage.  The adjacent intact mucosal epithelium contains numerous transmigrating neutrophils in all layers, has prominent intercellular clear spaces with accentuated intercellular bridging (spongiosis), and contains numerous keratinocytes that are swollen and have a single to numerous intracytoplasmic pale vacuoles (hydropic degeneration).  The lamina propria subjacent to the vesicle contains a superficial and perivascular inflammatory infiltrate composed of moderate to high numbers of viable neutrophils and fewer macrophages with mild hemorrhage, fibrin, and moderate edema.  The blood vessels associated with the lamina proprial inflammatory infiltrates are lined by cuboidal, hypertrophic (reactive) endothelial cells.  Additionally, there are few scattered 100x200um diameter protozoal cysts within the skeletal myocytes that have a prominent, 7 um-thick, hyalinized cyst wall and contain numerous crescentic, 3 x 15-20 um bradyzoites.  There are numerous filamentous chains and paired cocci within the superficial mucosal stratum corneum.

 

MORPHOLOGIC DIAGNOSES: 

1. Tongue:  Glossitis, vesiculopustular and neutrophilic, multifocal to coalescing, marked, acute, with marked intramucosal edema, Kudu (Tragelaphus sp.), artiodactyl.

2. Tongue, skeletal muscle: Intramyocytic protozoal cysts, few, etiology consistent with Sarcocystis sp.

 

ETIOLOGIC DIAGNOSIS:  Aphthoviral glossitis

 

CAUSE:  Foot and mouth disease virus (Aphthovirus)

 

CONDITION:  Foot-and-mouth disease (FMD)

 

GENERAL DISCUSSION:

• The most contagious disease of livestock; affects cattle, sheep, swine, goats and more than 70 species of wild animals causing high morbidity (100%) and low mortality (1%)
• Non-enveloped ssRNA virus in the genus Aphthovirus, family Picornaviridae; has seven serotypes: A, O, C types, Asia-1, South African Territory (SAT)-1, SAT-2, and SAT-3 with over 70 subtypes with no cross protection
  • Virulence varies with strain (>70 naturally occurring) and species affected
  • Antigenic variation and instability contribute to persistent nature
  • Antigenic drift demonstrated experimentally
• Inactivated at pH <6.0 or >9.0, heat sensitive (>50°C), inactivated by direct sunlight
• Virus survives for months in refrigerated tissues, hides, blood, hay, and other fomites
• Disease spread via movement of infected animals, contaminated animal products, and fomites; can be transmitted up to 250 km by wind

 

PATHOGENESIS:

• Capsid proteins (VP1-4): attachment proteins important in the antigenic & immunogenic properties of virus
• α integrins (Vβ1, Vβ3, Vβ6): receptors on target cells
• Ingestion or aerosol exposure > initial viral replication in pharynx and lung (respiratory epithelium, mucous membranes & lymphoid tissue of larynx and tonsils) > targets lymphoid cells, macrophages, dendritic cells > leukocyte trafficking to regional lymph nodes > replication phase in lymph nodes > systemic spread > lysis of epithelial cells in the stratum spinosum of stratified squamous epithelium
• Large amounts of virus in vesicular fluid, body secretions/excretions, skin/visceral tissues (esp. pancreas and pituitary gland), exhaled air (esp. pigs), and milk
• Antibody production: viremia/fever resolve > lesions heal > virus disappears
• Secondary bacterial infections common
• Carrier state can exist in some species: Water buffalo (only non-domestic species identified) and previously vaccinated cattle

 

TYPICAL CLINICAL FINDINGS:

• Salivation, nasal discharge, lameness
• Lethargy, fever, decreased milk production, and blanching of coronary bands may precede vesicles
• Pregnant animals may abort
• Sudden death in young animals with no typical vesicular lesions from viral myocarditis – mainly interventricular septum
• Sequelae: Hoof deformation, decreased milk production, chronic mastitis, unthriftiness, failure to thrive, diabetes mellitus

 

TYPICAL GROSS FINDINGS:

• Gross lesions alone cannot differentiate the vesiculoulcerative entities
• Early: vesicles on the nasal planum, oral cavity, oral mucosa (esp.tongue)
• Hyperemic foci on oral mucosa, udder (especially teats of lactating animals), and feet along coronary band 2-7 days post infection
• Develop into vesicles > coalesce to form bullae > rupture leaving raw ulcers; shreds of epithelium may adhere to edges
• Hooves may slough
• Vulva, prepuce, conjunctiva, esophagus, forestomachs, intestines, trachea, and bronchi may be involved
• Gray/yellow myocardial streaking (“tiger heart”) in animals less than 6 months of age; similar lesions may be present in skeletal muscle

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Early swelling, necrosis, and lysis of affected keratinocytes in the deep layer of the epidermis; extensive spongiosis of stratum spinosum
• Necrosis of overlying keratinocytes; rupture of vesicles to form erosions/ulcers, often with secondary bacterial overgrowth
• Mild leukocytic infiltration around erosions
• Microscopic vesicles in haired skin of brisket, abdomen, neck, carpus, and perineum
• “Dry” lesions in oral mucosa in which edema seeps through stratum corneum; now vesicles; mucosa appears necrotic
• Acinar necrosis in mammary tissue
• Hyaline degeneration, necrosis, and calcification of heart and skeletal muscle
• Mononuclear & necrotizing myocarditis and myositis in young animals
• Loss of pancreatic islets, acinar necrosis, and regeneration

 

ADDITIONAL DIAGNOSTIC TESTS:

• Viral antigen and nucleic acid detection
• Virus isolation
• Serology
• Reverse transcriptase PCR

 

DIFFERENTIAL DIAGNOSIS in cattle:

• Gross (oral lesions):
  • Vesicular stomatitis (rhabdovirus), vesicular exanthema of swine (genus vesivirus; family calicivirus), and swine vesicular disease (genus enterovirus; family picornaviridae): Indistinguishable from FMD
  • Bovine viral diarrhea (BVD)/mucosal disease (bovine pestivirus): Not  vesicular, linear esophageal ulcers, Peyer’s patch necrosis
  • Infectious bovine rhinotracheitis (bovine herpesvirus 1): Not vesicular, fibrinonecrotic rhinotracheitis      
  • Malignant catarrhal fever (alcelaphine herpesvirus-1, ovine herpesvirus-2): Not vesicular, corneal edema (“blue eye”), conjunctivitis, profuse mucopurulent nasal discharge
  • Rinderpest (morbillivirus): No vesicle, necrotic stomatitis, enteritis, Peyers patch
• Gross (foot lesions):
  • Contagious foot rot of ruminants (Dichelobacter nodosus): No oral lesions, not vesicular, +/- Fusobacterium necrophorum
  • Hairy heel warts, foot warts, strawberry foot, raspberry heel, papillomatous digital dermatitis (Treponema ): No oral lesions, not vesicular
  • Chemical burns or trauma to hooves: No oral lesions, not vesicular
  • Vesicular stomatitis, vesicular exanthema of swine, and swine vesicular disease: Indistinguishable from foot-and-mouth disease
  • BVD: Not vesicular, chronic digital dermatitis

 

COMPARATIVE PATHOLOGY:

FMD in other species:

• Cloven-hoofed animals especially susceptible & natural infection has been reported in domestic & wild ruminants, camelids, elephants, and swine, as well as hedgehogs; Cattle are indicator hosts; infections have also been documented in captive Asian black bears and sun bears
• Sheep/goats less susceptible than cattle; dental pad common site of erosions; mild lameness may be only clinical sign; carrier state exists; maintenance host
• Pigs: foot lesions more common than oral lesions; carrier state not observed in swine; abortion and stillbirth reported; swine are amplifier hosts

 

Other Vesicular Stomatitides:

Disease	Cause	Ruminant	Swine	Horse
Foot-and-mouth disease	Aphthovirus	+	+	--
Swine vesicular disease	Enterovirus	--	+	--
Vesicular stomatitis	Rhabdovirus	+ *	+	+
Vesicular exanthema of swine	Calicivirus	--	+	--
Seneca virus	Senecavirus	--	+	--

 

• *Vesicular stomatitis in ruminants: common in calves; does not occur in sheep or goats
• Senecavirus A (SVA) in pigs: presents with similar characteristics; mild clinical lesions and signs; cutaneous vesicles that rupture to form ulcers on lips, snout, tongue, and feet (Segales, Vet Pathol. 2017)

 

REFERENCES:

1. Agnew D, Nofs S, Delaney MA, et al. Xenartha, Erinacoemorpha, some Afrotheria, and Phloidota. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:527-8.
2. Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery, and peritoneal cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:340, 345-346,391.
3. Jimenez Martinez, MA, Gasper DJ, Carmona Mucino MdC, et al. Suidae and Tayassuidae. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:214.
4. Jones MEB, Gasper DJ, Mitchell E. Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:128-9.
5. Keel MK, Terio KA, McAloose D. Canidae, Ursidae, and Ailuridae. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:242-3.
6. Landolfi JA, Terrell SP. Proboscidae. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:424.
7. Segales J, Barcellos D, Alfieri A, Burrough E, Marthaler D. Senecavirus A: An Emerging Pathogen Causing Vesicular Disease and Mortality in Pigs? Vet Pathol. 2017:54(1):11-21.
8. Spickler AR, Roth JA. Emerging and Exotic Diseases of Animals. 3rd ed. Ames, IA: Iowa State University, 2008: 163-164, 262-265.
9. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, eds. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016: 117-119.

• Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:203.

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