JPC SYSTEMIC PATHOLOGY
Signalment (JPC # 2019293): Two-year-old, female Yorkshire Terrier
HISTORY: This dog was debilitated with labored respiration and a low-grade, persistent fever.
HISTOPATHOLOGIC DESCRIPTION: Urinary bladder: Diffusely transitional epithelial cells are swollen, have increased cytoplasmic clear space and vesiculate nuclei (degeneration) and contain one or more 2-6 micron round, eosinophilic intranuclear and intracytoplasmic viral inclusions. Rarely, individual epithelial cells are necrotic, characterized by shrunken hypereosinophilic cytoplasm and nuclear pyknosis.
Lung: Affecting approximately 60% of this section are multifocal areas of necrosis characterized by loss of alveolar architecture and replacement by eosinophilic cellular and karyorrhectic debris. Remaining alveoli are often filled with fibrin, macrophages, lymphocytes, plasma cells, neutrophils, sloughed epithelium, and cellular debris. Alveolar septa are expanded up to 5 times normal by fibrin, edema, moderate numbers of macrophages, fewer neutrophils and lymphocytes and are occasionally lined by cuboidal pneumocytes (type II pneumocyte hyperplasia). Multifocally there is necrosis of bronchiolar epithelium and remaining epithelium is often attenuated. Multifocally bronchiolar epithelial cells, alveolar macrophages, and type II pneumocytes contain variably sized (2-6 um), round, brightly eosinophilic intranuclear and intracytoplasmic viral inclusions. Respiratory epithelial cells occasionally coalesce and form viral syncytia. Occasionally interstitial and alveolar macrophages contain numerous 2-3 um round basophilic, intracytoplasmic protozoal tachyzoites. Multifocally peribronchiolar and perivascular connective tissue is mildly expanded by fibrin, edema, macrophages, fewer neutrophils, lymphocytes and plasma cells.
- Urinary bladder, transitional epithelium: Degeneration and necrosis, diffuse, with intraepithelial eosinophilic intracytoplasmic and intranuclear viral inclusions, etiology consistent with canine Morbillivirus, Yorkshire terrier, canine
- Lung: Pneumonia, bronchointerstitial, necrotizing, subacute, diffuse, severe, with syncytia and eosinophilic intracytoplasmic and intranuclear viral inclusions, etiology consistent with canine Morbillivirus, and intrahistiocytic tachyzoites, etiology consistent with Toxoplasma gondii
- Morbilliviral transitional epithelial necrosis
- Morbilliviral pneumonia and pulmonary toxoplasmosis
ETIOLOGY: Canine Morbillivirus; Toxoplasma gondii
SYNONYMS: Canine distemper; Canine Distemper Virus (CDV)
- Canine distemper is an important, ubiquitous infectious disease of dogs, other canidae, wild felidae, mustelidae, and pinnipeds worldwide
- CDV belongs to the genus Morbillivirus in the Paramyxoviridae family
- One recognized serotype; variable strain pathogenicity and tissue tropism
- Closely related to Rinderpest, peste de petit ruminants, measles, and phocine distemper viruses
- Negative-sense, single-stranded, enveloped RNA virus 150-300 nm in diameter
- Pantropic virus, entry into cells appears to be CD 150 (SLAM) mediated
- Virus has fusion glycoproteins which causes cells to fuse into syncitia; attachment protein, called viral H protein, and fusion protein, called viral F protein, that allow attachment to cell receptors
- Natural transmission is usually by inhalaion, and the virus is shed in all excretions during the systemic phase of infection
- Toxoplasmosis, neosporosis, coccidiosis, viral enteritis, cryptosporidiosis, giardiasis and canine adenovirus type 2 are common sequelae to the immunosuppressive effects of CDV
- Also causes Multifocal Distemper Encephalomyelitis in dogs infected at 4-8 years of age and Old Dog Encephalitis as a long-term subclinical infection
- See also systemics Nervous-V11, Pulmonary-V01 and Integument-V12
- Inhalation > virus replication in tonsils and bronchial lymph nodes > cell associated viremia 2 days PI > spread to all lymphoreticular tissues and blood lymphocytes one week PI > lymphocytolysis and leukopenia > immunosupression > dissemination to respiratory, GI, urinary, and central nervous systems; skin, endocrine and exocrine glands also affected > secondary infections common
- Dogs with adequate humoral and cell-mediated immunity recover with inapparent to moderate clinical signs within 14 days; dogs with intermediate or poor immunity develop severe, often terminal, disease
- Puppies that survive in utero infections may experience permanent immunodeficiency because of damage that occurs in primordial lymphoid elements
- Systemic disease affecting respiratory, gastrointestinal and nervous systems
- Biphasic fever, depression, anorexia, lymphopenia, serous to mucopurulent oculonasal discharge, pharyngitis, coughing, vomiting, diarrhea, hyperkeratosis of foot pads and nose, enamel hypoplasia, nervous signs
TYPICAL GROSS FINDINGS:
- Urinary tract: Gross lesions not observed
- Respiratory system: thick, foamy serous to mucopurulent hemorrhagic exudate in the airways
- Edematous and/or consolidated lungs, interstitial pneumonia, and serous pleural effusion
- Mucopurulent oculonasal discharge
- Lymphoid system: Tonsillar enlargement, thymus atrophy
- Integument system: Hyperkeratosis of the nose and footpad (“hardpad disease”); pustular dermatitis, in dogs associated with better clinical prognosis
- Digestive: Enamel hypoplasia
- Nervous: Multifocal necrotizing nonsuppurative encephalitis
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Eosinophilic intracytoplasmic and intranuclear inclusion bodies in epithelium (many locations, especially urinary bladder and lymphoid tissue) and syncytial cells
- Urinary bladder: Intracytoplasmic inclusions with rare intranuclear inclusions in transitional epithelium of urinary bladder and renal pelvis; epithelium of collecting tubules may also contain inclusion bodies
- Transitional epithelial cells are often swollen
- Epithelium in renal pelvis and bladder may contain congested vessels
- Cytoplasmic inclusions resembling CDV have been found in the urinary bladder of normal dogs
- Other tissues:
- Lung: Bronchointerstitial pneumonia with type II pneumocytes forming syncytia that often contain eosinophilic intracytoplasmic inclusion bodies
- Lymphoid tissues: Lymphocytolysis/lymphoid depletion in spleen, lymph nodes and thymus
- Skin: Parakeratotic hyperkeratosis of nose and footpads
- Eyes: Optic neuritis, degeneration/necrosis of retinal ganglion cells, retinitis, keratitis, conjunctivitis, anterior uveitis
- CNS: Variable spongiosis and demyelination, nonsuppurative encephalitis, perivascular cuffing, neuronal necrosis and inclusion bodies in astrocytes that occasionally form syncytia
- Toxoplasmosis often occurs in association with canine distemper
- Cytoplasmic inclusions consist of non-membrane bound aggregates of tubular viral nucleocapsids and cellular debris; similar tubular structures may be seen in the nucleus (despite lack of viral replication within the nucleus)
- Destruction of ensheathing myelin envelope in CNS
ADDITIONAL DIAGNOSTIC TESTS:
- CDV antigens demonstrated with immunoperoxidase technique
- CDV in epithelial cells by fluorescent antibody test or by virus isolation
- Non-specific inclusions that may be seen in the urinary bladder epithelium / pelvic urothelium in dogs
|DISEASE||NATURAL HOSTS||EXPERIMENTAL INFECTION|
Macaque; marmoset; mouse; hamster; rat
Cattle; pig; goat; sheep; buffalo; warthog; wildebeest; others
Goat; cattle; pig; deer
Peste des petits ruminants
Goat; sheep; gazelle; ibex; gemsbok
Goat; cattle; pig; deer
Dog; mink; seal
Canine distemper virus
Seal; Canidae; Mustelidae; Procyonidae (raccoon, coati, etc); Felidae; Suidae;
Dog; mouse; rat; hamster; mink; pig; cat; NHP; ferret
Cattle; sheep; goat; dog
Cattle; sheep; goat; dog
- Large cats, especially lions are very susceptible
- Mustelids (ferret, mink) very susceptible
- Large outbreak among rhesus monkeys in China in 2006 with up to 30% mortality
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- Qiu W, Zheng Y, Zhang S, et al. Canine distemper outbreak in rhesus monkeys, China. Emerg Infect Dis. 2011;17(8):1541-1543.
- Techangamsuwan S, Banlunara W, Radtanakatikanon A, Sommanustweechai A, Siriaroonrat B, Lombardini ED, Rungsipipat A. Pathologic and Molecular Virologic Characterization of a Canine Distemper Outbreak in Farmed Civets. Vet Pathol. 2015 Jul;52(4):724-31.
- Wenzlow N, Plattet P, Wittek R, Zurbriggen A, Groene A. Immunohistochemical demonstration of the putative canine distemper virus receptor CD150 in dogs with and without distemper. Vet Pathol 2007;44:943-948.
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