JPC SYSTEMIC PATHOLOGY
Signalment: (JPC #1848605): Breed and age unspecified goat
MICROSCOPIC DESCRIPTION: Mucocutaneous junction, lip (per contributor): Multifocally, there is epidermal hyperplasia with acanthosis (up to 10× normal thickness) and elongated, anastomosing rete ridges. Multifocally within the stratum spinosum, keratinocytes are markedly swollen and often contain clear intracytoplasmic vacuoles (ballooning degeneration) and pyknotic nuclei. Multifocally, keratinocytes contain one or more 2-10um, round to oval, brightly eosinophilic intracytoplasmic viral inclusion bodies. Within the superficial stratum spinosum and stratum corneum, there is neutrophilic exocytosis and multifocal clusters of neutrophils admixed with cellular and karyorrhectic debris, and abundant serum (microabscesses). There is minimal multifocal spongiosis of the epidermis. Overlying the affected epidermis is mild erosion with replacement by a thick serocellular crust composed of keratin, protein fluid, degenerate neutrophils and numerous mixed bacteria. Within the dermis there are numerous dilated small caliber blood vessels and lymphatics separated by clear space (edema), fibrin, and moderate numbers of perivascular neutrophils, histiocytes and lymphocytes.
MORPHOLOGIC DIAGNOSIS: Mucocutaneous junction, lip (per contributor): Cheilitis, proliferative and erosive, focally extensive, moderate, with epithelial eosinophilic intracytoplasmic viral inclusion bodies, serocellular crust and intraepidermal microabscesses, breed unspecified, caprine.
ETIOLOGY: Ovine parapoxvirus (orf virus)
ETIOLOGIC DIAGNOSIS: Parapoxviral dermatitis
CONDITION: Contagious ecthyma
SYNONYMS: Contagious pustular dermatitis, soremouth, orf (Old English for "rough"), infectious labial dermatitis, scabby mouth, lippengrind, farmyard pox (human)
- Contagious ecthyma (orf) is a common localized infection of young sheep and goats caused by ovine parapoxvirus (orf virus; ORFV) commonly leading to high morbidity and usually low mortality
- Disease is geographically widespread and occurs wherever sheep and goats are raised
- Orf virus (family Poxviridae, subfamily Chordopoxvirinae, genus Parapoxvirus) is a large (220‑300 x 140‑170 nm), enveloped, highly epitheliotropic, double stranded DNA virus
- Cattle, wild ungulates, humans and rarely dogs can be infected
- Transmission - direct contact; carrier animals; fomites (e.g. feed troughs, tail docking and ear tagging equipment, and emasculators)
- Disease usually resolves in 3-6 weeks; lesions are not contagious once scabs fall off, but scabs remain highly infective for long periods; the virus can survive at room temperature for 15 years
- Damage to the skin is necessary for infection - virus enters and replicates in cytoplasm of epidermal cells
- Host inflammatory response - CD4+, CD8+ T cells, B cells, dendritic cells and neutrophils. CD4+ T cells, interferons, antibodies - especially important to contain infection
- Orf virus encodes for several factors that help it evade the host immune response:
- Viral vascular endothelial growth factor (VEGF) - stimulates capillary proliferation, induces vascular permeability, and enhances epithelial proliferation
- Orf virus cytokine IL-10 orthologue - IL-10 suppresses recruitment and activation of neutrophils, monocytes and lymphocytes
- Orf virus interferon resistance gene (OVIFNR) - inhibits IFN-inducible dsRNA dependent kinase (PKR)
- Through the CD95 pathway, ORFV can initiate apoptosis in antigen producing cells and inhibit Bcl-2 (B-cell lymphoma 2) to prevent apoptosis of virus infected cells
TYPICAL CLINICAL FINDINGS
- Generally affects suckling lambs and kids; they contaminate teats and udders of dams and, thus spread the virus among siblings
- High morbidity (up to 100%); low mortality (rarely exceeds 1%); death occurs when lesions extend into the respiratory system
- Weight loss due to reluctance to eat because of oral and perioral lesions
TYPICAL GROSS FINDINGS
- Lesions begin at commissures of the mouth, then spread to lips, oral mucosa, tongue, eyelids, feet, and udders
- Cutaneous poxviral lesion development – macule > papule > vesicle > umbilicated pustule > crust > scar
- With contagious ecthyma (orf), the vesicle stage is very brief; ulcer and crust stages are clinically prominent
- Lesions may be invaded by larvae of screwworm fly (Cochliomyia hominivorax) or by Fusobacterium necrophorum or Dermatophilus congolensis
Rarely, lesions may extend into the alimentary and respiratory tracts, causing severe gastroenteritis and bronchopneumonia
TYPICAL MICROSCOPIC FINDINGS
- Marked epidermal hyperplasia with accentuated rete ridge formation; reticular degeneration; intraepidermal microabscesses; stratum spinosum keratinocytes are swollen and vacuolated; thick crust composed of orthokeratotic and parakeratotic hyperkeratosis, proteinaceous fluid, degenerate neutrophils and bacteria
- Newly proliferating keratinocytes in the outer stratum spinosum are the target-cell population for parapoxvirus infection; basophilic cytoplasm in swollen keratinocytes corresponds to polyribosome proliferation and viral replication
- Intracytoplasmic inclusion bodies – basophilic intracytoplasmic inclusion bodies can be seen by 36 hours post infection (p.i.); by 72 hours p.i., keratinocytes may have eosinophilic intracytoplasmic inclusions, pyknotic nuclei and marked hydropic change (ballooning degeneration) and large, multiloculated intraepidermal vesicles (reticular degeneration); by 55 hours p.i. numerous mitotic figures are present in the stratum basale; by 3 day p.i. epithelium is 3-4× normal thickness with elongate rete ridge formation
- Pseudocarcinomatous hyperplasia - common
- Dermis - superficial edema; vascular proliferation and dilation; perivascular mononuclear infiltrate
- Viral ulcerative dermatosis - disease of sheep caused by an 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
- Blue tongue (orbivirus) - affects adults more than lambs and causes a severe systemic illness with high mortality and low morbidity
- Sheeppox (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
- The International Committee on Taxonomy of Viruses (ICTV) currently (2009) recognizes 4 parapox viruses:
- Bovine papular stomatitis virus
- Orf virus
- Parapoxvirus of red deer in New Zealand
- Psuedocowpox virus
- Unassigned members in the genus include:
- Squirrel pox
- Pseudocowpox virus - chronic infection of milking herds; ring or horseshoe scabs on teats and on the muzzles and mouths of nursing calves
- Bovine papular stomatitis virus - affects animals less than 2 years of age; lesions on the muzzle, lip margins and buccal mucosa - similar to pseudocowpox
- Sealpox virus – ulcerative to proliferative, nodular, lesions at base of tongue, within oropharynx, along soft palate (zoonotic)
- Auzduk disease virus – camel contagious ecthyma virus
- Chamois (Rupicapra rupicapra) contagious ecthyma virus – wild goat contagious ecthyma virus
- Squirrel poxvirus – often fatal parapox infection of red squirrels
- Humans - orf virus is zoonotic; solitary lesions develop from macular to papular lesions to large nodules that, in some cases, become papillomatous; called milker's nodules (if acquired from cows) or orf (if acquired from sheep or wild artiodactyls)
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