JPC SYSTEMIC PATHOLOGY
Signalment (AFIP #1947253) (Slide A): 3-week-old kitten, breed and sex unspecified
HISTORY: One of three kittens that died within 24 hours of exhibiting open mouth breathing and lethargy
Lung: Over 90% of bronchial, bronchiolar and alveolar epithelium is replaced by eosinophilic cellular and basophilic karyorrhectic debris (lytic necrosis). There is marked septal necrosis with replacement and thickening of alveolar septa by fibrin, necrotic debris, hemorrhage, edema and increased numbers of macrophages and lymphocytes. The basement membranes surrounding smooth muscle and connective tissue of bronchioles and bronchi are multifocally lost, replaced by necrosis and fibrin and expanded by edema and small amounts of hemorrhage. Rare epithelial cells and macrophages contain round, eosinophilic, 4-7 um, intranuclear viral inclusion bodies that marginate the chromatin. The interstitium surrounding bronchi, bronchioles and vessels is expanded by fibrin, edema, hemorrhage and necrotic debris which contains moderate numbers of neutrophils and macrophages. Alveolar lumina, and to a lesser extent bronchi and bronchiolar lumina contain varying amounts of: fibrin, edema, degenerate neutrophils, necrotic debris, sloughed epithelial cells, few macrophages. The pleura is mildly expanded by fibrin, edema, necrotic debris, degenerate neutrophils and few macrophages.
Liver: There are multifocal, pinpoint, less than 90um diameter, random foci of hepatocellular lytic necrosis characterized by cells with condensed, hypereosinophilic cytoplasm and pyknotic to karyolytic nuclei. Hepatocytes adjacent affected areas are degenerate and rarely contain round, eosinophilic, 4-7 um, intranuclear viral inclusion bodies that marginate the chromatin.
MORPHOLOGIC DIAGNOSES: 1. Lung: Pneumonia, bronchointerstitial, fibrinonecrotic, acute, diffuse, with rare epithelial and histiocytic eosinophilic intranuclear viral inclusion bodies, breed unspecified, feline.
- Liver: Hepatitis, necrotizing, acute, multifocal and random, with eosinophilic intranuclear viral inclusion bodies.
Signalment (AFIP #963777) (Slide B): 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 epithelium and goblet cells with replacement by necrotic cellular debris, fibrin, hemorrhage, and numerous degenerate and transmigrating neutrophils. Adjacent degenerate epithelial cells are occasionally swollen with abundant clear cytoplasm and nuclei which contain round, eosinophilic, 4-7um, 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 contain an exudate composed of many neutrophils admixed with sloughed epithelial cells and fibrin.
MORPHOLOGIC DIAGNOSIS: Nasal turbinates and sinuses: Rhinitis and sinusitis, necrotizing and suppurative, subacute, multifocal, moderate, with eosinophilic intranuclear viral inclusion bodies, breed unspecified, feline.
ETIOLOGIC DIAGNOSIS: Feline herpesviral pneumonia, hepatitis, rhinitis, and sinusitis
CAUSE: Felid herpesvirus-1 (FHV-1)
CONDITION: Feline viral rhinotracheitis (FVR)
- 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
- Felid herpesvirus-1 usually causes an 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
- 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 > +/- recrudescent > 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 lymphoid nodes > infects additional cells there > systemic spread via leukocyte trafficking or cell-free viremia > infects a variety of cells > necrosis
- Disease may be exacerbated by secondary bacterial infection
- Cats that have presumably recovered may act as carriers (latently infected)
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
- Oral ulceration is rare
- Regional lymph nodes may become enlarged and congested
- Systemic infection 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
- 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
- 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:
- Virus isolation, IFA, PCR, In situ hybridization, immunohistochemistry
Rhinitis and conjunctivitis:
- Feline calicivirus (ssRNA): Oral ulceration; mild respiratory/conjunctival disease; similar pathogenesis to FHV and may be a co-infection
- Chlamydophila felis: Obligate intracellular bacteria; conjunctivitis, mild respiratory disease
- Mycoplasma felis: Opportunistic pathogen
- Bordetella bronchiseptica: Aerobic, gram negative coccobacillus; bronchopneumonia
- Feline calicivirus: Typically a milder pneumonia, less necrotizing; no inclusions
Skin lesions (ulcerative dermatitis):
- Mosquito bite hypersensitivity; eosinophilic reaction patterns; squamous cell carcinoma; allergic dermatitis
- Captive cheetah cubs: FHV-1 causes facial ulcers; necrosuppurative dermatitis with plasma cells, eosinophils, and intranuclear inclusion bodies within in the epithelium
- Bovine herpesvirus 1 (BoHV-1): Infectious bovine rhinotracheitis (IBR); infectious pustular vulvovaginitis; and infectious balanoposthitis
- BoHV-2: Bovine mammillitis virus; pseudo-lumpy skin disease
- BoHV-5: Bovine herpesvirus encephalitis
- Equid herpesvirus 1(EqHV-1): Equine herpesviral abortion, rhinopneumonitis, neurologic disease
- EqHV-3: Equine coital exanthema
- EqHV-4: Equine rhinopneumonitis, abortion
- Suid herpesvirus 1 (SuHV-1): Pseudorabies, Aujeszky’s disease
- 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
- Gallid herpesvirus 1: Avian infectious laryngotracheitis (ILT)
- Gallid herpesvirus 2: Marek's disease
- Psittacid herpesvirus 1: Pacheco’s disease
- Anatid herpesvirus 1: Duck plague
- Nonhuman primate:
- Herpesvirus simiae (Cercopithecine herpesvirus 1; B virus): Herpes B
- Herpesvirus tamarinus (Herpesvirus saimiri-1; Herpes T): Localized disease in squirrel monkeys; generalized disease in marmosets, tamarins, owl monkeys
- Herpesvirus simplex, type 1: Oral lesions in humans, apes, monkeys
- Herpesvirus simplex, type 2: Genital lesions in humans, apes, monkeys
- Simian varicella: Simian varicella in macaques, African green monkeys, Patas monkeys
- Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol. 2, 6th ed. St. Louis, MO: Elsevier; 2016:588-589.
- Hargis, AM, Myers S. The Integument. In: Zachary JF ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:1069, 1142-1143.
- Labelle P. The Eye. In: Zachary JF ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017: 1316
- Zachary JF. Mechanisms of microbial infections. In: Zachary JF ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017: 212.
- Pesavento PA, Murphy BG. Common and Emerging Infectious Diseases in the Animal Shelter. Vet Pathol. 2014;51(2):478-491.
- Rodriguez JMM, Leeming G, Kohler K, Kipar A. Feline herpesvirus pneumonia: investigations into the pathogenesis. Vet Pathol. On-line-first, electronic publication https://doi.org/10.1177/0300985817720982 2017.