JPC SYSTEMIC PATHOLOGY
Signalment (AFIP ACCESSION # 87-650): 3-week-old foal
HISTORY: Found dead.
HISTOPATHOLOGIC DESCRIPTION: D-B06a: Liver: Multifocally and randomly affecting approximately 70% of the hepatic parenchyma, there are numerous, coalescing, up to 1 mm in diameter foci of lytic necrosis and inflammation, characterized by replacement of parenchyma with eosinophilic cellular and karyorrhectic debris, admixed with fibrin, edema, hemorrhage, and few entrapped individualized hepatocytes. These areas are rimmed by large numbers of viable and degenerate neutrophils and fewer macrophages and lymphocytes. Adjacent hepatocytes are swollen with pale, vacuolated cytoplasm (degeneration), or are shrunken and hypereosinophilic with pyknotic nuclei (necrosis), or have retention of cellular architecture and loss of differential staining (coagulative necrosis). Peripheral, less affected hepatocytes often contain numerous stacked, pale, basophilic, filamentous (1x 5um) bacilli. Portal areas and the subcapsular space are expanded up to three times normal by ectatic lymphatic vessels (edema), hemorrhage, fibrin, and low numbers of lymphocytes, plasma cells, macrophages, and rare neutrophils , and have increased bile duct profiles (biliary ductular reaction).
D-B06b: Liver (Warthin-Starry, pH 4.0): Within hepatocytes at the periphery of necrotic areas are many argyrophilic, filamentous bacilli. Bacilli occur in parallel and perpendicular sheaves and bundles as well as individually. Occasionally bacilli are free within necrotic debris.
MORPHOLOGIC DIAGNOSIS: Liver: Hepatitis, random, suppurative, necrotizing, acute, multifocal to coalescing, severe, with intracellular argyrophilic bacilli, breed not specified, equine.
ETIOLOGIC DIAGNOSIS: Clostridial hepatitis
CAUSE: Clostridium piliforme (previously Bacillus piliformis)
SYNONYMS: Tyzzer's disease
- Acute, fatal, enterohepatic disease of young or immunocompromised animals of many species, primarily recognized in laboratory rodents, rabbits, foals, dogs and cats; can also affect other species
- Bacterial strain differences may occur between hosts
- Characterized by sudden death with or without diarrhea
- Infection is more common in weanling, debilitated, or immunocompromised animals; stress associated with overcrowding, shipping, breeding, or high temperatures is thought to predispose animals to infection
- Classic triad of target tissues: Liver, intestine, heart
- Clostridium piliforme is a pleomorphic, gram-negative (the only gram negative of the pathogenic clostridia), obligate intracellular, spore-forming rod
- Vegetative form:
- Bacteria look like “bundles” or “sheaves” within cells
- Active stage responsible for disease
- Extremely labile outside the host
- Spore form:
- Not easily seen in tissue
- Responsible for transmission by fecal-oral route
- Can survive up to a year at room temperature (i.e. in contaminated bedding)
- Most isolates are host specific; some appear to be cross-infective
- Exact mechanism of spread from ingestion to the liver is unclear
- Transmission of Clostridium piliforme is fecal-oral > carried by normal peristaltic activities through the oral pharynx, esophagus, and stomach to the small intestine (ileum) > gain access to the intestinal mucosal epithelium > bacteria spread via portal circulation to liver > colonization of hepatic parenchyma > multifocal necrosis
- In rodents, experimental transplacental transmission has been reported
TYPICAL CLINICAL FINDINGS:
- Peracute disease with sudden death in weanling and young animals (foals 7-42 days old)
- Elevated liver enzymes; leukopenia
TYPICAL GROSS FINDINGS:
- Icterus, hepatic enlargement with multiple pinpoint to miliary gray foci
- Necrotizing enteritis with marked congestion and edema
- Occasional white linear bands in myocardium
- Hemorrhagic and edematous lymph nodes
TYPICAL MICROSCOPIC FINDINGS:
- Multifocal to coalescing irregular areas of hepatic necrosis, often surrounded by hemorrhage, macrophages and neutrophils
- Parallel or crisscrossed bundles or stacks of faintly staining bacilli (on H&E) in cytoplasm of hepatocytes at margins of necrotic foci
- Necrotizing enterocolitis described in foals and other species
- Foci of myocardial necrosis
- Bacilli in cytoplasm of cells
- Vegetative forms have numerous peritrichous flagella (flagella distributed over the entire cell surface).
ADDITIONAL DIAGNOSTIC TESTS:
- Silver stains - Warthin Starry (4.0) or Steiner's
- Also demonstrated with Methylene blue, Giemsa, GMS
- Will not grow on cell free media
For random necrotizing hepatitis in foals:
- Equine herpesvirus I: Hepatic necrosis, concurrent interstitial pneumonia, intranuclear inclusion bodies in hepatocytes
- Salmonella sp. or coli septicemia: Watery, foul smelling diarrhea, joint lesions, pneumonia and/or meningitis (with Salmonella sp); differentiate by bacterial morphology and stains
- Sleepy foal disease (Actinobacillus equuli): Multifocal hepatitis, severe enteritis, embolic nephritis; differentiate by bacterial morphology and stains
- Reported in laboratory mice, rats, lagomorphs, rhesus monkeys, gerbils, guinea pigs, hamsters, cats, horses, canids, calves, birds, otters, whitetail deer, ferrets
- Rats: Megaloileitis, necrotizing ileitis, hepatic necrosis and hepatitis, linear myocardial necrosis
- Rabbits: Miliary foci throughout the liver, linear myocardial necrosis, edema and necrotizing mucosal colitis
- Guinea pigs: Necrotizing ileitis and typhlitis, focal periportal hepatic necrosis and NO myocardial lesions
- Hamsters: Hepatic necrosis, enteritis, granulomatous myocarditis
- Mongolian gerbil especially susceptible; used as a sentinel in research facilities
- Pinpoint foci of necrosis in liver, necrotizing ileitis and typhlitis, focal myocardial necrosis, encephalitis
- Cats: Associated with feline infectious peritonitis virus; feline leukemia virus infection in kittens; one report in kittens with feline panleukopenia virus; one case report concurrent with feline rhinotracheitis
- Avian: Few reported cases of Tyzzer’s disease; one reported case of encephalitis caused by Clostridium piliforme
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, Iowa: Blackwell Publishing; 2016: 53-54,137-138, 181-182, 201-203, 225, 275-276.
- Cullin JM, Stalker MJ. Liver and biliary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 2. Philadephia, PA: Elseveier; 2016:317-318.
- Jenkins JR, Oglesbee BL. Gastrointestinal diseases. In: Carpenter JW, Quesenberry KE, eds. Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery. St Louis, MO: Elsevier Saunders; 2012:199-200.
- Mete A, Eigenheer A, Goodnight A, Woods L. Clostridium piliforme encephalitis in a weaver bird (Ploceus castaneiceps). J Vet Diagn Invest. 2011; 23: 1240-1242.
- Neto RT, Uzal FA, Hodzic E, Persiani M, Jolissaint S, et al. Coinfection with Clostridium piliforme and Felid herpesvirus 1 in a kitten. J Vet Diagn Invest. 2015; 27(4):547-51.
- Pearson EG. Tyzzer’s Disease in Foals. In: Smith B, ed. Large Animal Internal Medicine. 4th ed. St. Louis, Missouri: Mosby; 2009:902.
- Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 2. Philadephia, PA: Elseveier; 2016 :99, 113-114, 183-194.
- Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:166-167.