JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
November 2022
I-V03
Signalment (JPC# 1851279): 10‑day‑old budgerigar (Melopsittacus undulatus)
HISTORY: This bird was from a flock with increased mortality in birds under 15 days of age.
SLIDE A:
HISTOPATHOLOGIC DESCRIPTION: Feathered skin: Multifocally, individual and clusters of keratinocytes within the epidermis and feather follicle epithelium are swollen and contain abundant, microvacuolated, pale eosinophilic cytoplasm (hydropic degeneration). Nuclei of these cells are enlarged and often contain variably shaped, up to 20µm diameter, indistinct, pale amphophilic or clear to glassy intranuclear viral inclusion bodies that marginates the chromatin. Diffusely there is moderate orthokeratotic hyperkeratosis.
MORPHOLOGIC DIAGNOSIS: Feathered skin, epidermal and follicular epithelium: Hydropic degeneration, multifocal, moderate, with moderate orthokeratotic hyperkeratosis and amphophilic intranuclear viral inclusion bodies, budgerigar, avian.
ETIOLOGIC DIAGNOSIS: Polyomaviral dermatitis
SLIDE B:
HISTOPATHOLOGIC DESCRIPTION: Kidney: The interstitium is multifocally expanded by moderate hemorrhage as well as few lymphocytes, plasma cells and macrophages. Multifocally, tubular epithelial cells and glomerular mesangial cells are enlarged with karyomegalic nuclei that contain round to oval, up to 20µm diameter, indistinct, pale eosinophilic to amphophilic to clear, glassy intranuclear viral inclusion bodies that marginate the chromatin. Multifocally, tubular epithelial cells are swollen with vacuolated cytoplasm (degenerate) or less frequently are shrunken with hypereosinophilic cytoplasm and pyknotic or karyorrhectic nuclei (necrotic). Tubules occasionally contain sloughed cellular and karyorrhectic debris (cellular or granular cast).
MORPHOLOGIC DIAGNOSIS: Kidney: Nephritis, interstitial, lymphohistiocytic, mild, chronic, with tubular degeneration and necrosis, and tubular and mesangial cell intranuclear viral inclusion bodies, budgerigar, avian.
ETIOLOGIC DIAGNOSIS: Polyomaviral nephritis
ETIOLOGY: Avian polyomavirus (APV)
CONDITION: Budgerigar fledgling disease (BFD)
GENERAL DISCUSSION:
- Avian polyomavirus is a non-enveloped, dsDNA virus in the family Polyomaviridae (previously Papovaviridae)
- BFD is a pansystemic disease of nestling budgerigars and other psittacines
- Most common lesions are feather loss and dysplasia, hepatic necrosis, hemorrhage, and a membranous glomerulopathy with karyomegaly with intraunuclear inclusions in hepatocytes, renal tubular epithelium, splenic periarteriole sheeths, and others
- Severity of feather changes, necrosis, hemorrhage, and presence of intranuclear inclusion bodies variable depending on species
- Lesions in budgerigars and non-budgerigar psittacines are different, but proven to be the same polyomavirus; also infects green aracaris, causing fatal disease
PATHOGENESIS:
- Virus shed in droppings, oral secretions, and feather/skin dander
- Transmission is likely via inhalation; speculated that vertical transmission can occur
- Once infected, become viremic with virus present in nearly all organs; shedding follows shortly after in both asymptomatic and symptomatic birds
- Concurrent psittacine beak and feather disease (PBFDV, a circovirus) common – will see gross and histologic lesions consistent with both diseases; may predispose adult birds to APV due to immunosuppression
- Glomerulopathy occurs due to type III hypersensitivity reaction (viral antigen and immunoglobulin Y or, less often, immunoglobulin M); deposition of immune complexes may be severe enough to occlude glomerular capillary lumens
TYPICAL CLINICAL FINDINGS:
- Most birds are asymptomatic
- Disease and death mostly confined to nestling budgies (10-20 days old) and nestling parrots (>14 weeks old), especially macaws, conures, caiaues, eclectus parrots, lovebirds, and ring necked parrots
- Outbreaks in adults have occurred, but are rare (eclectus parrots, caiques, and lovebirds)
- May see intention tremors in budgies with cerebellar lesions
- Cockatoos – chronic illness, grow poorly, emaciation
TYPICAL GROSS FINDINGS:
- Nestling budgie
- Stunted, abnormal or delayed growth and feather development; discolored skin; +/- hemorrhage within feather shafts; budgies that survive will lack or have dystrophic (thickened) contour feathers, flight feathers, and/or down (or any combination of the three)
- Other: Abdominal distension with hepatomegaly with multifocal necrosis (pale pin-point foci), herihepatic effusion to ascites; cardiomegaly, hydropericardium; and widespread scattered petechial hemorrhage; +/- renal swelling; enlarged, hemorrhagic bursa of Fabricius; splenomegaly with hemorrhage; pancreatitis; general tissue pallor
- Most other psittacines
- Excellent overall condition (developed normally; feather changes rare)
- Other: Striking subcutaneous and serosal hemorrhage with generalized tissue pallor (due to blood loss); hepatomegaly with necrosis; splenomegaly; epicardial petechial and ecchymotic hemorrhage; anasarca and ascites (secondary to protein losing nephropathy or decreased albumin production from hepatic necrosis)
- Amazon parrots, African gray parrots, and cockatoos usually unaffected or generally have a less severe disease; however, with cockatoos, more likely to see moist lungs with decreased buoyancy compared to other birds
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Intranuclear inclusion bodies (INIB, Cowdry Type B) that are large, glassy, clear to pale basophilic, granular and marginate chromatin, causing karyomegally
- Inclusions may be present in the spleen, liver, kidney, lung, heart, brain, adrenal gland, skin, feather follicle, intestine, trachea, esophagus, crop, bursa of Fabricius, and proventriculus
- Skin: Massive infection of follicular germinal epithelium, nearly within every cell of the zone of differentiation, with minimal inflammation; ballooning degeneration, epithelial karyomegaly with INIB’s
- Kidney: Membranous glomerulopathy; karyomegally (tubular and glomerular mesangial) with INIB’s (mesangial, endothelial and tubular epithelial cells); mesangial cell necrosis and glomerular capillary vacuolation;
- If they survive the acute infection, can cause chronic renal disease and glomerulosclerosis
- Spleen: Lymphoid depletion, multifocal periarteriole sheath necrosis and INIBs (macrophage and splenic reticular cells)
- Liver: Random multifocal to midzonal to massive hepatic necrosis with hemorrhage, karyomegally with inclusions (hepatocytes, Kupffer cells)
- Budgies usually have random necrosis; non-budgerigar psittacines frequently have severe midzonal massive hepatocellular necrosis, except cockatoos usually have none
- INIB’s are infrequent in cockatiels compared to others
- Can be superimposed over chronic-active hepatitis, which is common in birds
- Heart: Myocardial degeneration and coagulative necrosis, hemorrhage, lymphoplasmacytic inflammation, karyomegally of myocytes with INIB
- Lung: In most birds, typically unaffected, but may see interstitial mononuclear inflammation with rare INIB’s; in cockatoos, see diffuse interstitial pneumonia, type II pneumocyte hyperplasia, severe pulmonary edema, and numerous viral inclusions
- Brain: Variable cerebellar non-suppurative encephalitis targeting Purkinje cells (budgies); gray matter hemorrhage and degeneration of astrocytes; INIB most common in molecular layer of cerebellum
- Bursa: lymphoid depletion and necrosis with INIB in lymphocytes
- Skeletal muscle: myofiber necrosis, INIB
ULTRASTRUCTURAL FINDINGS:
- Virions: naked, icosahedral, 42-48nm (much smaller than adenovirus)
ADDITIONAL DIAGNOSTIC TESTS:
- PCR, immunohistochemistry, in situ hybridization, immunoflourescent staining, electron microscopy, virus isolation
- PAS can be used to highlight glomerulopathy
DIFFERENTIAL DIAGNOSIS:
Gross
- Acute death in young birds: Herpesvirus (Pacheco’s disease, D-V13, H-V03; also has hepatic necrosis with deep basophilic INIB), chlamydiosis (Chlamydophila psittaci, D-B12), salmonellosis or other bacterial septicemias, Psittacine beak and feather disease (PBFD, circovirus, I-V04), lead poisoning, psittacine adenovirus, and reovirus infections
- Feather lesions: Psittacine beak and feather disease (PBFD, avian circovirus, I-V04) – identical gross presentation; histologically, see ICIB, epidermal collar necrosis/apoptosis
Microscopic
- Intranuclear inclusions: Herpesviruses (Pacheco’s disease) and circoviruses (PBFD) may produce amphophilic to basophilic intranuclear inclusions; avian adenoviruses may produce karyomegaly and darkly eosinophilic to basophilic intranuclear inclusions (commonly found, but usually incidental)
- Hepatic necrosis and splenomegaly: Herpesvirus (Pacheco’s disease), adenovirus, chlamydiosis (Chlamydophila psittaci), salmonellosis or other bacterial septicemias
COMPARATIVE PATHOLOGY:
- There have been at least 7 polyomaviruses discovered in birds including APV (discussed here), canary polyomavirus, finch polyomavirus, crow polyomavirus, butcherbird polyomavirus
- Finch polyomavirus: Gouldian finches and other pet birds
- Causes apathy, diarrhea, high mortality in nestlings; gross lesions included liver enlargement, pulmonary congestion, and urate accretions in the kidney; microscopic findings included Cowdry type B intranuclear inclusion bodies; PCR detected polyomavirus (Circella J Comp Pathol 2017)
- Rarely infects beak germinal epithelium resulting in inflammation, necrosis, INIB’s, and narrowing/elongation of the beak in finches
- One report of a Sertoli cell tumor with polyomavirus INIB’s within neoplastic cells, but causality was not confirmed
- Polyomaviruses are typically of little or no significance other species (i.e. asymptomatic); characteristic intranuclear inclusions seen in various tissues
- NHP: Simian virus 40 (U-V09 – nephritis, pneumonia, and neurologic disease in severely immunocompromised [e.g. SIV infected] macaques); cynomolgus polyomavirus; baboon polyomavirus 1 and 2, human BK and JC viruses
- Mice:
- Murine polyomavirus (PyV): Multifocal necrosis and inflammation in immunodeficient mice (neonatal or nude) followed by tumor formation in multiple tissues; multisystemic wasting disease with paralysis and demyelination also reported in nude mice
- K-Virus (murine pneumotropic virus or Kilham polyomavirus): Carried as a latent infection in mice; strong tropism for pulmonary endothelium; oronasal transmission with hematogenous dissemination and replication in pulmonary vascular endothelium, leading to pulmonary edema, hemorrhage, and eventual death; no oncogenic properties
- Hamster: Hamster polyomavirus (HaPyV) causes multiple tumors, including:
- Transmissible/epizootic lymphoma in young hamsters; the lymphoma does NOT have detectable infectious HaPyV (no INIB’s), but does have HaPyV nucleic acid in their genome and often Type C retroviral particles
- Keratinizing skin tumors of hair follicles (trichoepitheliomas); can occur with epizootic infections, but more common with enzootic infection of adult hamsters; skin tumors DO have viral replication in keratinizing epithelium
- Infected adults are typically asymptomatic carriers (spreading virus in the urine)
- Rat: Rat polyomavirus (Rat-PyV) causes wasting disease, dyspnea with pneumonia, and parotid sialadenitis in athymic nude rats; INIB are prominent in the salivary gland epithelium of both symptomatic and asymptomatic rats
- Rabbit: Rabbit kidney vacuolating virus causes intranuclear inclusions in renal tubular epithelium; no known pathogenic effect and non-oncogenic
- Raccoon: Raccoon polyomavirus (RacPyV) causes neuroglial brain tumors in the olfactory tract and bulb; the viral oncogenic gene Large T antigen is present within the genome of tumor cells
References:
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley and Sons, Inc. 2016: 19-21, 122, 176-178, 197, 261.
- Church ME, Terio KA, Keel MK. Procyonidae, Viverridae, Hyenidae, Herpestidae, Eupleridae, and Prionodontidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier. 2018: 309.
- Delaney MA, Treuting PM, Rothenburger JL. Rodentia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier. 2018: 506-507.
- Circella E, Caroli A, Marino M, et al. Polyomavirus Infection in Gouldian Finches (Erythrura gouldiae) and Other Pet Birds of the Family Estrildidae. J Comp Pathol. 2017;156:436-439.
- Gibson DJ, Nemeth NM, Beaufere H, et al. Development and use of a triplex real-time PCR assay for detection of three DNA viruses in psittacine birds. J Vet Diagn Invest. 2019;31(5):719-725.
- Reavill DR, Dorrestein G. Psittacines, Coliiformes, Musophagiformes, Cuculiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier. 2018: 786-787, 788.
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