JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2156896): Tissue from a sheep
HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocally centering around bronchioles are consolidated nodules (pocks) up to 2mm in diameter composed of alveoli lined by hyperplastic type II pneumocytes and alveolar lumina filled with eosinophilc fluid and hemorrhage, degenerate neutrophils and necrotic debris, lymphocytes and plasma cells, and moderate numbers of macrophages with vesiculate nuclei and abundant amphophilic foamy cytoplasm containing one or more round to oval, 2‑8um diameter, pale eosinophilic intracytoplasmic viral inclusion bodies (sheeppox cells). The bronchioles in the center of the nodules are lined by hyperplastic epithelium that is piled up to five layers deep with transmigrating degenerate neutrophils, and bronchiolar epithelial cells occasionally contain 2-4um diameter eosinophilic intracytoplasmic viral inclusion bodies. Multifocally bronchioles contain a small amount of fibrinous exudate. The majority of the remaining alveolar septa are mildly expanded by lymphocytes, macrophages, and neutrophils. There is mild perivascular edema and the vascular endothelium is hyperplastic.
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, bronchointerstitial, proliferative, subacute, multifocal, moderate, with nodular type II pneumocyte hyperplasia, intrahistiocytic eosinophilic intracytoplasmic viral inclusion bodies (sheeppox cells), and intraepithelial eosinophilic intracytoplasmic viral inclusion bodies, breed unspecified, ovine.
ETIOLOGIC DIAGNOSIS: Capripoxviral pneumonia
CAUSE: Sheeppox virus (Capripoxvirus, ovine strain)
- Capripoxvirus (subfamily Chordopoxvirinae; family Poxviridae) – Double stranded DNA virus with complex ovoid or brick shaped virons
- Acute to chronic, contagious, systemic disease characterized by generalized pox lesions throughout the skin (especially sparsely wooled areas) and mucous membranes, persistent fever, lymphadenitis, and often pneumonia
- Bi‑seasonal (winter and summer); endemic in North Africa, Asia, and the Middle East; exotic to the Americas, Australia and New Zealand; OIE list A disease
- Occurs in all ages, but most severe in young lambs, with high mortality (80‑100%, 50% in adults)
- Fine‑wooled sheep (Merinos) are especially sensitive; breeds native to endemic areas are more resistant to infection
- Extensive losses result from high mortality in lambs, abortions and mastitis in ewes, and skin defects
- The virus is resistant to desiccation and may remain viable in wool for 2 months or in dried crusts for up to 6 months
- Sheeppox and goatpox are the most virulent of the pox diseases, and cause systemic illness
- Introduction of virus into skin or respiratory tract > local viral replication in epidermis, dermis, or respiratory epithelium (epitheliotropic) > regional lymph nodes via macrophages > replicates in cytoplasm of epithelial cells, mucosal lymphocytes and macrophages, and dendritic cells > exits via efferent lymphatics into blood
- Cell-associated viremia occurs causing extensive vasculitis in arterioles and post‑capillary venules (immune‑mediated complex deposition), thrombosis and ischemic necrosis with intense infiltration of neutrophils; virus has not been identified in endothelial cells
- Stomoxys calcitrans (stable fly) is an efficient mechanical vector of capripox
- Sheeppox cells are CD14 and CD172a positive (antigens expressed on monocytes and macrophages)
- Pock lesions mainly composed of hyperplastic type II pneumocytes (positive for: TTF-1 (transcription protein of type II pneumocytes and club [formerly Clara] cells); proliferating cell nuclear antigen (PCNA) involved in DNA replication during S phase; and Surfactant protein (SP) A, B, and proSP-C)
TYPICAL CLINICAL FINDINGS:
- Fever, seromucous oculonasal discharge, increased respiratory rate, eyelid edema, salivation and hyperesthesia
- Vesicular stage: Generalized prominent, umbilicated, multilocular vesicles and cutaneous nodules (0.5‑1.5 cm in diameter)
- Pustular phase: Coalescing vesicles covered by a thin crust
- Death is usually due to secondary bacterial infections (septicemia and/or pneumonia); in animals that recover, the lesions ultimately heal, leaving permanent depressed scars
TYPICAL GROSS FINDINGS:
- Most lesions (vesicles, nodules, ulcerations and crusts) are confined to sparsely wooled skin and mucous membranes
- Disseminated white nodules in the lung
- Prominent vesicular stage followed by a pustule stage with thin crusts and gelatinous dermal edema
- One-third of the animals develop respiratory lesions presenting as miliary foci of consolidation as the result of hematogenous infection
- Mediastinal lymph nodes are often significantly enlarged, congested, hemorrhagic, and edematous
- Renal lesions consist of multifocal, circular, fleshy nodules throughout cortex
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Cutaneous lesions:
- Surface epithelium and follicles with marked hydropic degeneration, acanthosis, microvesiculation, eosinophilic intracytoplasmic viral inclusion bodies (ICIB), hemorrhage, and pustule formation
- Extensive dermal edema during the papular phase, and the accumulation of large numbers of mononuclear cells around blood vessels and between collagen bundles; these cells (sheeppox cells, cellules claveleuses of Borrel) have vacuolated cytoplasm with ICIB and vacuolated nuclei with marginated chromatin
- Sheeppox cells are virus-infected monocytes, macrophages, and fibroblasts, but not endothelial or epithelial cells
- Severe necrotizing vasculitis develops in arterioles and post-capillary venules resulting in dermal and epidermal ischemic necrosis
- Respiratory lesion:
- Pulmonary lesions include proliferation of virus containing bronchiolar epithelium and type II pneumocytes (proliferative alveolitis and bronchiolitis) with areas of focal caseous necrosis with infiltration of sheeppox cells, neutrophils and lymphocytes and formation of gland-like structures
- Alveolar septal and bronchiolar epithelial cells may contain ICIB
- May cause hyperplastic nodules in the trachea
- Additional lesions:
- Accumulation of sheeppox cells may involve heart, kidney, adrenals, thyroid, and pancreas
- Oval (brick shaped) virions measuring 220-300 X 140-170nm in cytoplasm of keratinocytes and macrophages
- Infected cell nuclei often have marginated chromatin and a central, less electron dense area with fine filaments arranged singly or in bundles
ADDITIONAL DIAGNOSTIC TESTS:
- Virus isolation from enlarged lymph nodes; Virus neutralization; Indirect fluorescent antibody
- Respiratory Lesions:
- Ovine Pulmonary Carcinomatosis (Betaretrovirus): Adenomatous change
- Ovine Progressive Pneumonia (Lentivirus; Retroviridae): Peribronchial and perivascular lymphoid hyperplasia, smooth muscle hyperplasia, minimal type II pneumocyte hyperplasia; no alveolar inflammation; no viral inclusions
- Parainfluenza type 3 (Paramyxovirus): Bronchointerstitial pneumonia with eosinophilic ICIB and occasional syncitial cells
- Epithelial Lesions:
- Ovine Foot and Mouth Disease (Aphthovirus; Picornavirus): Vesicles on feet and mucosa of dental pad
- Contagious ecthyma (Orf virus, Parapoxvirus): Lesions muzzle, eyelids, and teats; most sever in lambs and kids zoonotic
- Bluetongue (Orbivirus; Reoviridae): Nonpurulent conjunctivitis; congested and edematous muzzle; coronitis; deformed aborted fetuses
- Peste des Petits Ruminants (Morbillivirus; Paramyxoviridae): White, raised, necrotic oral lesions; pneumonia and diarrhea
- Goats: Goatpox - clinically similar disease;
- Cattle: lumpy skin disease (reportable) - ulcers in mouth, nares; circumscribed lesions in lungs and alimentary tract; Jersey and Guernsey most susceptible
- Orthopoxvirus: Camelpox, Cowpox, Ectromelia (mousepox), Monkeypox, Vaccinia (buffalopox, rabbitpox), Uasin Gishu disease virus
- Parapoxvirus: Bovine popular stomatitis, Orf, Parapox of red deer, Pseudocowpox, Sealpox, Camel and chamois contagious ecthyma
- Avipox: Fowlpox, Pigeonpox
- Leporipox: Myxoma, Rabbit (Shope) fibroma
- Suipox: Swinepox
- Molluscipox: Molluscum contagiosum
- Yatapox: Tanapox, Yaba monkey tumor
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