JPC SYSTEMIC PATHOLOGY
SIGNALMENT (JPC #1956094): 5-month-old lamb
HISTOPATHOLOGIC DESCRIPTION: Tongue: Multifocally, the hyperplastic epithelium is expanded up to 500 um and contains numerous various sized pustules with many degenerate neutrophils, fewer macrophages, lymphocytes, and plasma cells admixed with hemorrhage, fibrin and edema. Multifocally, the pustules are ruptured and the superficial epithelium is eroded and covered in a disorganized coagulum of karyorrhectic and cellular necrotic debris and degenerate neutrophils. Adjacent keratinocytes are swollen with abundant pale eosinophilic to clear vacuolated cytoplasm (hydropic degeneration) and multifocally contain 5-10 um diameter, round, eosinophilic intracytoplasmic viral inclusion bodies. Multifocally, individual keratinocytes are shrunken with bright eosinophilic cytoplasm and karyorrhexis, karyolysis, or nuclear pyknosis (necrosis). Hemorrhage, fibrin, edema and low to moderate numbers of neutrophils, lymphocytes and macrophages moderately expand the adjacent subepithelial connective tissue and separate, surround, and expand the perimysium and endomysium of underlying skeletal muscle bundles and fibers, respectively. There is a moderate increase in subepithelial, small caliber vessels which are frequently lined by hypertrophied, reactive endothelium. Multifocally, individual myocytes are swollen with vacuolated sarcoplasm (degeneration) or shrunken with bright eosinophilic cytoplasm, disorganization of myofibrils, loss of cross striations and absent or pyknotic nuclei (necrosis). Multifocally expanding skeletal myofibers are thin-walled protozoal cysts up to 80 um in diameter containing numerous crescentic basophilic bradyzoites (sarcocysts). On the epithelial surface and within the stratum corneum, there are multiple colonies of 1 x 3 um filamentous bacilli.
- Tongue: Glossitis, proliferative and necrotizing, multifocal, moderate, with hydropic degeneration, intraepithelial pustules, and epithelial eosinophilic intracytoplasmic viral inclusion bodies, breed not specified, ovine.
- Tongue, skeletal muscle: Intramuscular protozoal cysts, multiple, etiology consistent with Sarcocystis sp.
ETIOLOGY: Ovine parapoxvirus (family Poxviridae, genus Parapoxvirus)
ETIOLOGIC DIAGNOSIS: Ovine parapoxviral glossitis and glossal sarcocystosis
CONDITION: Contagious ecthyma (CE)
SYNONYMS: Orf (human condition), contagious pustular dermatitis (stomatitis), sore mouth, scabby mouth
- Family: Poxviridae, Genus: Parapoxvirus are ovoid and have a regular surface, whereas other poxviruses are large, pleomorphic or brick-shaped
- Genome is linear, double stranded DNA
- Worldwide distribution with a broad host range to include sheep, goats, humans
- Ovine parapoxvirus is closely related to the parapoxviruses causing pseudocowpox and bovine papular stomatitis
- Predominantly a disease of lambs and kids that produces proliferative cutaneous, mucocutaneous and oral lesions resulting in high morbidity, low mortality
- Secondary bacterial infections (Fusobacterium necrophorum, Dermatophilus congolensis), fly strike, extension of the virus into the lung, or when oral lesions are severe enough to prevent nursing
- Resolution of uncomplicated disease takes approximately 2-4 weeks
- Very hardy virus; persists for extended periods of time on wool and indefinitely in crust material and in the environment
- “orf” - Old English for “rough”
- Viral transmission via fomites from ruptured vesicles, scabs, and direct contact from infected animals
- Viral entry via small skin abrasions > infects Langerhan’s cells and capillary endothelium > virus uses F1L envelope protein to bind to heparin sulfate receptors on host cells > subsequent viral replication in epithelial cells > papule formation due to epithelial ancatholysis and cytolysis > progresses to a vesicle and/or pustule that forms a thick brown/black scab over the original lesion > reparative and regenerative response contributes to epithelial hyperplasia
- Virulence factors:
- Vascular endothelial growth factor (VEGF) is an important virulence factor
- Increase vascular permeability, capillary growth and epidermal hyperplasia increase viral replication and crust formation
- CD95 induced apoptosis of antigen presenting cells
- Bcl-2 inhibition of apoptosis in virally infected cells
- Vascular endothelial growth factor (VEGF) is an important virulence factor
- Dry and prickly pasture or forage can abrade the oral mucosa allowing viral entry
- Ulcerated lesions allow entry of secondary pathogens
- Zoonotic through entry of infected exudates through skin abrasions
TYPICAL GROSS FINDINGS:
- Elevated brown-black to gray crusts are the most significant gross and clinical feature
- Typical pox lesions of proliferative and ulcerative dermatitis; however these tend to be more proliferative
- Vesicles are brief and transient; pustules are flat rather than umbilicated
- Lesions start at lip commissures with spread to the muzzle and nostrils
- Lesions may develop on gingiva, dental pad, palate, tongue, udder, teats, coronary bands, interdigital cleft, heel bulb, anus, esophagus, and rumen
- Buccal lesions are raised, red or gray foci with surrounding zone of hyperemia
- Lesions may be spread to ewe's udder through nursing of lamb
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Vacuolation and swelling of keratinocytes in the outer stratum spinosum, hydropic (ballooning) degeneration, marked epidermal proliferation with elongated rete ridges, intraepidermal microabscesses, and accumulation of an overlying scaly crust
- By 72 hours, eosinophilic intracytoplasmic inclusion bodies appear; inclusion bodies persist as long as hydropic cells are present, which is typically 3-4 days
- Oval virions measuring 220-300 x 140-170 nm in cytoplasm of keratinocytes
- Infected cell nuclei often have marginated chromatin and a central, less electron dense area with fine filaments arranged individually or in bundles
ADDITIONAL DIAGNOSTIC TESTS:
- Electron microscopic examination of tissue for virus
- Grossly for oral lesions:
- Sheep pox (Poxviridae, capripoxvirus): High mortality, reportable disease; elevated papules in sparsely wooled areas; systemic disease (esp. pneumonia); inclusions common; less proliferative than parapoxvirus
- Ulcerative dermatosis (unclassified poxvirus): Ulcerated papules on the lips, face, legs, feet, and genitalia; no epithelial hyperplasia
- Foot and mouth disease (Picornaviridae, aphthovirus): Must be considered if lesions are confined to the tongue/buccal mucosa
- Grossly for skin lesions:
- Ulcerative dermatosis (unclassified poxvirus): spread is by direct contact especially during breeding
- Balanoposthitis - vulvitis is commonly seen in the fall breeding season
- Mycotic dermatitis - usually occurs in woollen skin; scabs are smaller, thinner, lighter, and usually yellow; the crusts are not firmly attached
- Blue tongue (Orbivirus) - affects adults more than lambs and causes a severe systemic illness with high mortality and low morbidity
- Sheeppox (Poxviridae, capripoxvirus) - similar skin lesions with systemic lesions and a high mortality rate
- Orf lesions confined to the oral cavity may resemble foot and mouth disease
- Contagious echthyma has been reported in sheep, goats, cattle, camels, Dall sheep, gazelle, bighorn sheep, reindeer, musk ox, chamois, dogs, and cats
- Other parapoxviruses:
- Bovine papular stomatitis (Poxviridae, parapoxvirus): Papules in oral cavity of young cattle that must be differeniated from other more serious causes of ulcerative oral lesions; “pseudocowpox,” occasionally transferred to udder via suckling calves with lesions identical to "milker's nodule" in humans
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