JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

November 2025

I-V11

Signalment (JPC# 1848605): Breed and age unspecified goat

HISTORY: None

MICROSCOPIC DESCRIPTION: Mucocutaneous junction, lip (per contributor): Multifocally, the epidermis is expanded up to 10 times normal thickness by hyperplasia characterized by acanthosis; elongated, anastomosing rete ridges; and multifocal parakeratotic hyperkeratosis as well as minimal multifocal spongiosis. Multifocally within the stratum spinosum, keratinocytes are markedly swollen (ballooning degeneration) or are ruptured forming multilocular intraepidermal vesicles that contain eosinophilic edema fluid and are divided by resistant cell walls of ruptured epithelial cells (reticular degeneration). Multifocally, keratinocytes contain one or more 2-10 µm, round to oval, brightly eosinophilic, intracytoplasmic viral inclusion bodies. Within the stratum spinosum and stratum corneum, there is neutrophilic exocytosis and multifocal clusters of neutrophils admixed with cellular and karyorrhectic debris, and abundant serum (pustules/microabscesses). The affected epidermis is mildly eroded and overlain by a thick serocellular crust composed of keratin, proteinaceous fluid, necrotic neutrophils, foreign debris, and bacterial colonies. Within the dermis, small caliber blood vessels and lymphatics are dilated and separated by clear space (edema), fibrin, and there is moderate perivascular, superficial neutrophilic and lymphohistiocytic inflammation.

MORPHOLOGIC DIAGNOSIS: Mucocutaneous junction, lip (per contributor): Cheilitis, proliferative and erosive, neutrophilic, focally extensive, moderate, with epithelial intracytoplasmic viral inclusions, serocellular crust, and intraepidermal microabscesses, breed unspecified, caprine.

ETIOLOGY: Ovine parapoxvirus (orf virus [ORFV])

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)

GENERAL DISCUSSION:

• Contagious ecthyma (orf) is a common localized infection of young sheep and goats caused by ovine parapoxvirus (ORFV) commonly leading to high morbidity and usually low mortality
• Disease is geographically widespread and occurs wherever sheep and goats are raised
• Highly contagious and zoonotic
• ORFV (family Poxviridae, subfamily Chordopoxvirinae, genus Parapoxvirus) is a large (220‑300 nm x 140‑170 nm), enveloped, highly epitheliotropic, double stranded DNA virus

PATHOGENESIS

• 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; direct contact with fomites or crusts > virus enters Langerhans cells and endothelial cells > local viral replication and trafficking > endothelial cell dysfunction and death > epithelial cell damage (vesicles and pustules) > epithelial cell proliferation > proliferative and erosive stomatitis and dermatitis
• Host inflammatory response: CD4+, CD8+ T cells, B cells, dendritic cells, and neutrophils
  • CD4+ T cells, interferons, and antibodies are especially important to contain infection
• ORFV 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
  • ORFV cytokine IL-10 orthologue - IL-10 suppresses recruitment and activation of neutrophils, monocytes and lymphocytes
  • ORFV 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 🡪 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

• Epithelium
  • Marked epithelial hyperplasia with accentuated rete ridge formation; intraepithelial pustules and microabscesses; stratum spinosum keratinocytes are swollen (hydropic change, ballooning degeneration) and vacuolated (multiloculated intraepidermal vesicles, reticular degeneration); 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 (early inclusion bodies are basophilic and progress to typical eosinophilic intracytoplasmic inclusions
  • Pseudocarcinomatous hyperplasia - common
• Dermis - superficial edema; vascular proliferation and dilation; perivascular mononuclear infiltrate

DIFFERENTIAL DIAGNOSIS

Gross lesions

• 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; various etiologies
• Mycotic dermatitis - usually occurs in woollen skin
• Blue tongue (orbivirus, D-V16) - affects adults more than lambs and causes a severe systemic illness with high mortality and low morbidity
• Sheeppox (capripoxvirus, P-V24) - similar skin lesions with systemic lesions and a high mortality rate
• Foot and mouth disease (picornavirus, D-V17): Orf lesions confined to the oral cavity may resemble lesions of foot and mouth disease

COMPARATIVE PATHOLOGY

• ORFV: Can also infect cattle, wild ungulates, camelids, red squirrels (United Kingdom), seals, sea lions, humans, and rarely dogs
  • Humans - ORFV 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)
• Other parapox viruses: the International Committee on Taxonomy of Viruses (ICTV) currently (2018) recognizes 4 parapox viruses and several unassigned viruses:
  • 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
  • ORFV (described above)
  • Parapoxvirus of red deer in New Zealand-semi-domesticated reindeer (high mortality)
• Unassigned members in the genus parapoxvirus:
  • 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
  • Red squirrel parapoxvirus – often fatal parapox infection of red squirrels in the United Kingdom; grey squirrels are likely maintenance hosts

REFERENCES

1. Agnew, Dalen. Ch. 7 Camelidae In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018:195.
2. Delaney MA, Treuting PM, Rothenburger JL. Rodentia. In: Terio KA, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier Science Publishing Co Inc; 2018:506.
3. Jones ME, Gasper, DJ, Mitchell, Emily, et al. Ch. 5 Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018:125
4. Howerth EW, Nemeth NM, Ryser-Degiorgis MP. Cervidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:158.
5. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:616-618.
6. Pintus D, Cancedda MG, Puggioni G, et al. ORF virus causes tumor-promoting inflammation in sheep and goats. Vet Pathol. 2024;61(5):803-814.
7. Welle MM, Linder KE. The integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed., St. Louis, MO; Elsevier; 2022:134, 247-248, 277, 465, 1130, 1162-1163, 1224, 1226.

Click the slide to view.

---