JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V09

 

Slide A: Signalment (JPC #1947253): 3-week-old kitten, breed and sex unspecified

 

HISTORY: One of three kittens that died within 24 hours exhibiting open mouth breathing and lethargy

 

HISTOPATHOLOGIC DESCRIPTION:  

Lung: Over 90% of bronchial, bronchiolar, and alveolar epithelium is replaced by eosinophilic cellular and basophilic karyorrhectic debris (lytic necrosis). Over 90% of alveolar septa are lost and replaced and thickened by fibrin, necrotic debris, hemorrhage, edema, macrophages, and lymphocytes (septal necrosis). Rare epithelial cells and macrophages contain round, eosinophilic, 4-7 µm, intranuclear viral inclusion bodies that marginate the chromatin. The interstitium surrounding bronchi, bronchioles and vessels is expanded by fibrin, edema, hemorrhage, necrotic debris, and moderate numbers of neutrophils and macrophages. Alveolar lumina and to a lesser extent bronchial and bronchiolar lumina contain an exudate composed of varying amounts of: Fibrin, edema, degenerate neutrophils, necrotic debris, sloughed epithelial cells, and few macrophages. The pleura is mildly expanded by fibrin, edema, necrotic debris, degenerate neutrophils and few macrophages.

 

Liver: Affecting approximately 20% of the section are multifocal, random, pinpoint, less than 90 µm diameter, foci of hepatocellular necrosis characterized by hepatocytes with condensed, hypereosinophilic cytoplasm and pyknotic or karyolytic nuclei. Hepatocytes adjacent to necrotic foci are degenerate and rarely contain round, eosinophilic, 4-7 µm, intranuclear viral inclusion bodies that marginate the chromatin. 

 

MORPHOLOGIC DIAGNOSES:  

1. Lung: Pneumonia, bronchointerstitial, fibrinonecrotic, acute, diffuse, severe, with rare epithelial and histiocytic eosinophilic intranuclear viral inclusion bodies, breed unspecified, feline.

2.  Liver: Hepatitis, necrotizing, acute, multifocal and random, mild, with eosinophilic intranuclear viral inclusion bodies.

 

ETIOLOGIC DIAGNOSIS: Feline herpesviral pneumonia and hepatitis

 

Slide B: Signalment (JPC #963777): A kitten, breed and sex unspecified  

 

HISTORY: Died showing signs of respiratory distress

 

HISTOPATHOLOGIC DESCRIPTION: Nasal turbinates and sinuses: Multifocally, there is attenuation, erosion, and ulceration of ciliated nasal respiratory epithelium and goblet cells with replacement by necrotic cellular debris, fibrin, hemorrhage, and numerous degenerate neutrophils. Adjacent degenerate epithelial cells are occasionally swollen with abundant clear cytoplasm and nuclei which contain round, eosinophilic, 4-7µm, intranuclear viral inclusion bodies that marginate the chromatin. Many neutrophils with fewer macrophages and lymphocytes surround nasal glands and expand the submucosa, and vessels in affected areas are lined by reactive endothelium. Multifocally, sinuses and nasal meatuses contain an exudate composed of many neutrophils admixed with sloughed epithelial cells and fibrin.  

 

MORPHOLOGIC DIAGNOSIS: Nasal turbinates and sinuses: Rhinitis and sinusitis, necrosuppurative, subacute, multifocal, moderate, with eosinophilic intranuclear viral inclusion bodies, breed unspecified, feline.

 

ETIOLOGIC DIAGNOSIS: Feline herpesviral rhinitis and sinusitis

 

CAUSE: Felid herpesvirus-1 (FHV-1) 

 

CONDITION: Feline viral rhinotracheitis (FVR)

 

GENERAL DISCUSSION: 

• Felid herpesvirus-1 is a dsDNA alphaherpesvirus that is highly species specific causing upper respiratory disease, conjunctivitis, ulcerative keratitis, ulcerative dermatitis, ulcerative stomatitis, abortion, and chronic rhinitis and sinusitis in all domestic cats worldwide
• Single most important pathogen contributing to feline upper respiratory infection
• Rarely causes pneumonia or systemic disease, but can result in vasculitis and hemorrhage in multiple organs when it does 
• All species of felids are susceptible, especially young animals
• Like other alphaherpes viruses, causes cytolytic infections of mucosal epithelial cells
• Felid herpesvirus-1 usually causes acute self-limiting disease in naïve animals and establishes lifelong neural latency in trigeminal ganglion, optic nerve, olfactory bulb, and cornea
• Recrudescence can result in conjunctivitis, rhinosinusitis, and/or interstitial pneumonia 
• Morbidity is high; mortality tends to be low

 

PATHOGENESIS:

• Virus targets respiratory epithelium and pneumocytes
• Similar pathogenesis to infectious bovine rhinotracheitis and equine viral rhinopneumonitis
• Primary target cells are at sites with lower body temperature such as the corneal and conjunctival epithelium
• Uses viral envelope glycoprotein G to attach to and bind chemokine receptors on target cells 
• Transmission is by direct contact, infectious discharges, or aerosolization
• Virus invades mucosal epithelial cells (conjunctiva, cornea, nose, pharynx, trachea) > primary replication > virus release from cell causes cytopathic effect > epithelial erosion, ulceration, inflammation > viral spread from upper airways via trachea to the lungs resulting in pneumonia > death or recovery in 10-14 days and virus establishes lifelong latency in neurons of the trigeminal ganglia (quiescent, non-replicative phase) > stress > reactivation of virus > +/- recrudescence  > ocular or respiratory tract disease 
• Extensive necrosis results from virus-induced neutrophil influx and release of proteolytic enzymes such as MMP9 from neutrophils
• Viremia is uncommon; generalized disease (e.g. pneumonia, hepatitis, abortion) may occur in debilitated or young animals

• Viral infection of mucosal macrophages > spread to regional lymph nodes > infects additional cells there > systemic spread via leukocyte trafficking or cell-free viremia > infects a variety of cells > necrosis

• Cats that have presumably recovered may act as carriers (latently infected)
• Pulmonary involvement is uncommon, except in fatal cases; secondary bacterial bronchopneumonia is a more common complication vs a primary viral pneumonia.  

 

TYPICAL CLINICAL FINDINGS:

• Disease varies from subclinical to fatal
• Depression, sneezing, dyspnea, pyrexia
• Serous to mucopurulent oculonasal discharge
• Conjunctivitis with hyperemia and chemosis

 

TYPICAL GROSS FINDINGS:

• Conjunctivitis and occasionally ulcerative keratitis; dendritic ulcers
• Ulcerative dermatitis of the nasal planum, periorbital areas, and other haired facial skin resulting in ulcers, erosions, crusts 

• Rarely can be present on ear pinna

• Serous to mucopurulent exudate
• Oral ulceration is rare
• Regional lymph nodes may become enlarged and congested
• Systemic infection is uncommon, but may result in extensive rhinotracheitis, bronchointerstitial pneumonia, and multifocal necrosis of the liver, adrenal glands, and bone with petechial hemorrhages and vasculitis in multiple organs

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Large intranuclear inclusions within tracheal and bronchial respiratory epithelium that marginate the chromatin and are surrounded by a clear halo (Cowdry type A)

• Most numerous in the acute infection
• Rarely identified beyond 7 days post infection

• Rhinitis, sinusitis, conjunctivitis: Epithelial necrosis, neutrophilic inflammation, fibrinous exudate; occasional ulcerative keratitis
• Necrosis and resorption of turbinates may occur
• Viremia or generalized disease may result in necrotizing bronchointerstitial pneumonia, multifocal necrosis (liver, adrenal gland, bone)
• Ulcerative dermatitis with prominent eosinophilic inflammation

• Definitive skin diagnosis requires histologic identification of light basophilic intranuclear inclusion bodies with chromatin margination in intact epithelial cells
• Extensive necrosis of epidermis, follicles, and occasionally sebaceous glands
• The eosinophil-rich inflammatory pattern overlaps with that of hypersensitivity and eosinophilic ulcers

• Viral antigen is present in pneumocytes, alveolar macrophages, and necrotic bronchial and bronchiolar epithelial cells

 

ULTRASTRUCTURAL FINDINGS:

• Icosahedral virions that are approximately 108 nm (nonenveloped particles) or 180nm (enveloped particles) in diameter
• Virions assembled in the nucleus become enveloped as they bud from the nuclear membrane

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

Rhinitis and conjunctivitis:

• Feline calicivirus (ssRNA): Oral ulceration; mild respiratory/conjunctival disease; similar pathogenesis to FHV and may be a co-infection 
• Chlamydia felis: Obligate intracellular bacteria; conjunctivitis, mild respiratory disease
• Mycoplasma felis: Opportunistic pathogen

Pneumonia:

• Bordetella bronchiseptica: Aerobic, gram negative coccobacillus; bronchopneumonia
• Feline calicivirus: Typically a milder pneumonia, less necrotizing; no inclusions

Ulcerative dermatitis:  

 

COMPARATIVE PATHOLOGY:  

FHV-1 in other species:

Other alpha-herpesviruses:

• Bovine:

• Bovine herpesvirus 1 (BoHV-1): Infectious bovine rhinotracheitis (IBR); infectious pustular vulvovaginitis; and infectious balanoposthitis (R-V02)
• BoHV-2: Bovine mammillitis virus; pseudo-lumpy skin disease
• BoHV-5: Bovine herpesvirus encephalitis 

• Equine:

• Equid herpesvirus 1(EqHV-1 [P-V10]): Equine herpesviral abortion, rhinopneumonitis, neurologic disease
• EqHV-3: Equine coital exanthema
• EqHV-4: Equine rhinopneumonitis, abortion
• EqHV-5: Equine multinodular pulmonary fibrosis (P-V27)

• Porcine: Suid herpesvirus 1 (SuHV-1): Pseudorabies, Aujeszky’s disease
• Canine: Canid herpesvirus 1: Fatal generalized disease in newborn puppies with ulcerative tracheitis, interstitial pneumonia, focal necrosis and inflammation in the kidney, liver and brain; abortions and stillbirths
• Avian:

• Gallid herpesvirus 1: Avian infectious laryngotracheitis (ILT)
• Gallid herpesvirus 2 (N-V08): Marek's disease 
• Psittacid herpesvirus 1 (D-V13): Pacheco’s disease
• Anatid herpesvirus 1: Duck plague
• Columbid herpesvirus-1 (CoHV-1): infects raptors and pigeons

• Nonhuman primate:

• Herpesvirus simiae (Cercopithecine herpesvirus 1; B virus): Herpes B 
• Herpesvirus tamarinus (Herpesvirus saimiri-1; Herpes T [D-V14]): Localized disease in squirrel monkeys; generalized disease in marmosets, tamarins, owl monkeys
• Human herpesvirus simplex, type 1: Oral lesions in humans, apes, monkeys
• Human herpesvirus simplex, type 2: Genital lesions in humans, apes, monkeys
• Simian varicella (I-V16): Simian varicella in macaques, African green monkeys, Patas monkeys
• Varicellovirus (human alphaherpesvirus): Affects apes, similar lesions to chickenpox in children

• Cervidae:

• Cervid herpesvirus1 (CerHV-1)
• Cervid herpesvirus 2 (CerVH-2): Rangiferine, Ocular lesions and KCS

• Marsupials: Macropodid herpes virus (MaHV-1): rhinitis, conjunctivitis, pneumonia
• Pinnipediae (seals): Phocine herpesvirus-1 (PhHV-1): harbor and gray seals, adrenocortical and hepatic necrosis (young animals)
• Reptiles: All identified reptile herpesviruses are alphaherpesviruses

• Chelonia (turtles): Many distinct alphaherpesviruses with confusing and changing nomenclature; selected viruses of importance:

• Tortoise herpesvirus 1: Necrotizing stomatitis and glossitis with diphtheritic membrane formation
• Tortoise herpesvirus 2: Necrotizing stomatitis and glossitis as well as endotheliotropism > vasculitis, edema, thrombosis
• Fibropapillomatosis: Affects sea turtles, thought to be due to Chelonid herpesvirus 5

• Lacertilla (Lizards)

• Herpesvirus associated papillomas
• Iguanid herpesvirus 1: Asymptomatic to liver necrosis
• Varanid herpesvirus spp: Hepatitis and enteritis
• Gerrhosaurus herpes virus spp: Stomatitis and cheilitis

 

REFERENCES:

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