JPC SYSTEMIC PATHOLOGY
ENDOCRINE SYSTEM
February 2022
E-V01 (NP)

Signalment (JPC #1848505):  14-day-old Duroc pig   

HISTORY:  Suckling pigs and sows were sick.  Only the suckling pigs died following a disease characterized by anorexia, depression, diarrhea or constipation, and staggering gait.

HISTOPATHOLOGIC DESCRIPTION:  Adrenal gland: Affecting 10% of the section, including the cortex, medulla, and the corticomedullary junction, are multifocal to coalescing areas of lytic necrosis up to 500 um in diameter characterized by loss of normal architecture with replacement by eosinophilic cellular and karyorrhectic debris.  On the periphery of the necrotic foci, occasional cortical cells and fewer chromaffin cells contain 2-6 um, round to oval, eosinophilic, intranuclear viral inclusion bodies which marginate the chromatin. There is scattered single cell death characterized by cells that are shrunken and hypereosinophilic with pyknotic nuclei. There are few viable and degenerate neutrophils scattered within the cortex, minimal multifocal hemorrhage, fibrin, and edema, and rare mitotic figures within the zona glomerulosa.

Eye (not present on all slides): Diffusely replacing the corneal epithelium (ulceration) and the superficial 1/3 to 1/2 of the corneal stroma (keratitis) are focally extensive neutrophilic infiltrates admixed with abundant eosinophilic cellular and karyorrhectic necrotic debris and variably sized aggregates of basophilic, mixed bacteria. Remaining corneal stromal fibers are disorganized and often separated by increased clear space (edema), reactive fibroblasts, fewer lymphocytes and macrophages, and small caliber blood vessels (vascularization). Diffusely, the bulbar conjunctiva is similarly affected. Multifocally, there are colonies of 1 um diameter cocci along the conjunctival surface.

MORPHOLOGIC DIAGNOSIS:  1. Adrenal gland: Adrenalitis, necrotizing, acute, multifocal, random, moderate, with eosinophilic intranuclear viral inclusion bodies, Duroc, porcine.

2. Eye, cornea and bulbar conjunctiva: Keratoconjunctivitis, necrosuppurative, acute, diffuse, with corneal edema and vascularization.

ETIOLOGIC DIAGNOSIS:  Alphaherpesviral adrenal necrosis

CAUSE:  Suid herpesvirus 1 (SuHV-1)

CONDITION / SYNONYMS:  Pseudorabies; Aujeszky’s Disease; mad itch; infectious bulbar paralysis; porcine herpesvirus infection

GENERAL DISCUSSION: 

• This is primarily a disease of swine that can spread both vertically and horizontally, causing abortions and respiratory disease in older pigs and CNS signs in neonatal pigs (see N-V07)
• The virus lacks host specificity and can infect a wide range of secondary hosts in which it is lethal due to nonsuppurative meningoencephalomyelitis; secondary hosts include cattle (mad itch), sheep, dog (pseudo-rabies), cat, rabbit (lab animal spp), many feral species; rare in horses; humans are refractory
• Causes an intense pruritus in secondary hosts (“mad itch”) especially in cattle
• Endemic in swine (domestic and feral) worldwide
• Epitheliotropic and neurotropic
• Latent infections in trigeminal ganglion, olfactory bulb, and tonsil

PATHOGENESIS: 

• Transmission: Direct contact (contaminated saliva and nasal secretions), fomites or aerosol, inhalation or ingestion, abraded skin; regardless of route, virus found in nasal secretions; non-porcine/secondary carnivore hosts are infected through ingestion of infected pig meat and ruminants via direct contact, aerosol, or contaminated feed
• Inhalation: Primary viral replication in upper respiratory epithelium (pharynx, nasal cavity, tonsil)
  • Invades sensory nerve endings > transported in axoplasm to the olfactory bulb and up the trigeminal, glossopharyngeal, facial, and vagus nerves to cerebral interpretive centers; it causes a ganglioneuritis at many sites
  • The virus may also spread to the spinal cord and then to peripheral nerves, and may circulate in blood
  • Can also infect tonsils and lungs > viral dissemination either in free form or via infected leukocytes > visceral infection > nervous system invasion via autonomic nerves
• Inoculation: Local reaction > centripetal spread along nerve to spinal cord > outward spread along peripheral nerves and concurrent spread up spinal cord to the brain
• Ingestion (usually of infected pig meat): Transport across epithelium via M cells to mononuclear cells of Peyer's patches; also localizes in myenteric plexus > nervous system along autonomic nerves

TYPICAL CLINICAL FINDINGS:

• Neonatal and weaned piglets (<9 weeks old)
  • Very young piglets – rapid prostration and death with no premonitory signs
  • Older piglets – incoordination, paralysis, tremors, convulsions, and respiratory signs; may recover in 5-10 days
  • “Dog sitting” posture due to respiratory distress
  • Mortality may reach 100% in neonatal piglets infected in the first two weeks of life, decreasing to 50% in the 3^rd and 4^th weeks
• Grower-finisher and adult pigs: fever, rhinitis, coughing, and anorexia
• Sows: fetal resorption (<30 days gestation), mummification, stillbirth, or abortion
• Non-swine: Intense cutaneous pruritus and frenzy, fever, dogs may demonstrate jaw paralysis and drooling; typically results in death within 1-2 days (or before clinical signs develop)

TYPICAL GROSS FINDINGS: 

• May be minimal or absent; gross findings predominantly seen in young pigs
• Necrotizing rhinitis, tonsillitis, esophagitis, and tracheitis
• Tiny foci of hemorrhagic necrosis in the liver, spleen, lungs, intestines, placenta, and adrenal glands in suckling pigs
• Necrotizing endometritis, placentitis, oophoritis
• May see keratoconjunctivitis
• Epithelial necrosis, ballooning degeneration, serofibrinous inflammation with rare viral intranuclear viral inclusions at site of cutaneous infection (non-swine)

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Neurotropic lesions (more common in ruminants and carnivores)
  • Non-suppurative inflammatory lesions in the brain
  • Acidophilic intranuclear inclusions (INIBs) in neurons and astroglia
    • Solid and amphophilic in swine
    • Granular, small, and multiple in nuclei of other species
  • Marked perivascular cuffing with nonsuppurative meningoencephalitis, ganglioneuritis (in paravertebral ganglia)
  • Necrosis of neurons with neuronophagia and gliosis
  • Piglets develop panencephalitis, most severe in brainstem, cerebral cortex and spinal ganglia; in other species lesions dependent on route of exposure
• Epitheliotropic lesions (more common in young and aborted piglets)
  • Tiny areas of coagulative or lytic necrosis of liver, tonsils, lung, spleen, placenta, and adrenals with INIB’s; hemorrhage is variable
  • Adrenal glands: INIB’s, necrosis and hemorrhage of the cortex and medulla with lymphohistiocytic infiltrate in later stages
  • Lung: mild edema with diffuse cellular infiltrate to necrohemorrhagic pneumonia
  • Lymphoid necrosis
• Stillborn/aborted fetuses: no encephalitis; foci of necrosis in liver with bronchiolar necrosis and interstitial pneumonia

ULTRASTRUCTURAL FINDINGS:

• Approximately 180nm diameter virions with a nucleocapsid core surrounded by three concentric shells: inner, middle, and outer capsids; nonenveloped virions in the nucleus that acquire an envelope during passage through the nuclear membrane

ADDITIONAL DIAGNOSTIC TESTS: 

• Enzyme immunoassay, fluorescent antibody, virus isolation, IHC

DIFFERENTIAL DIAGNOSIS:

Adrenal cortical necrosis:

• Infectious agents: High concentration of local anti-inflammatory steroids in cortex > suppression of local cell-mediated immunity > preferential growth of fungi, bacteria, and protozoa > necrosis and inflammation
  • Protozoa (Toxoplasma gondii [E-P01], Neospora caninum, Sarcocystis spp.): focal necrosis with minimal inflammation
  • Bacterial septicemia: often gram negative organisms; focal necrosis and suppuration
  • Mycobacteria: cattle and humans
  • Systemic fungal organisms (Histoplasma capsulatum, Coccidiodes immitis, Cryptococcus neoformans): dogs and cats in endemic areas; cortical granulomas with cortical hypertrophy
  • Rickettsia rickettsii (Rocky Mountain Spotted Fever): dogs and people

COMPARATIVE PATHOLOGY: 

• Typically fatal in secondary hosts
• Transmission typically via ingestion
• Typically causes intense pruritus in secondary hosts - mad itch
• Nonsuppurative meningoencephalomyelitis: cattle, sheep, dogs, cats, rabbits (most susceptible lab animal), guinea pigs, raccoons, rats, mice, opossum, skunk
• Fatal degenerative angiopathy in mink (viremia and endotheliotropism)
• Rare reports in horses and goats

REFERENCES:    

1. Cantile C, Youssef S. Nervous system. In: Maxie MG , ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:370-372.
2. Izzati UZ, Kaneko Y, et al. Distribution of Pseudorabies Virus Antigen in Hunting Dogs with Concurrent Paragonimus wetermani infection. J Comp Pathol. 2021; 188: 44-51.
3. MacLachlan NJ, Dubovi EJ. Fenner’s Veterinary Virology. 5th ed. London, UK: Academic Press; 2017: 206-208.
4. Martinez MAJ, Gasper DJ, Muncino MdCC, et al. Suidae and Tayassuidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Cambridge, MA: Elsevier, 2018, 211-212.
5. Mettenleiter TC, Ehlers B, et al. Herpesviruses. In: Zimmerman JJ, Karriker LA, et al, eds., Disease of Swine. 11th ed., Ames, IA: Blackwell Publishing; 2019: 551-561.
6. Miller AD, Zachary JF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2016:889.
7. Rosol TJ, Grone A. Endocrine glands. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:340.
8. Schlafer DH, Foster RA. Female Genital System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:432.
9. Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2016: 224-225.

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