History
A 1-month-old quarter horse colt was presented for acute onset lethargy, loss of suckling, diarrhea, and seizure activity. The dam had received all recommended vaccinations, the foal’s birth was uneventful, and no concerning behaviors were noticed until this episode. The foal was on pasture with 4 other mares and 1 foal, all of which appeared healthy. The owners had lost 2 other foals of this age in a previous year.
Clinical and Gross Findings
Physical examination showed that the foal was dull, had an elevated rectal temperature (40.1 °C; reference interval [RI], 37.8 to 39.1 °C), heart rate (170 beats/min; RI, 60 to 80 beats/min), and respiratory rate (40 breaths/min; RI, 20 to 40 breaths/min). Mucus membranes and sclera were injected, the capillary refill time was < 2 seconds, and yellow-colored diarrhea stained the foal’s perineum and pelvic limbs. Point-of-care blood work showed hypoglycemia (64 mg/dL; RI, 70 to 135 mg/dL) and hyperlactatemia (7.2 mmol/L; RI, < 2.5 mmol/L). Abdominal ultrasound showed a fluid-filled colon and profoundly enlarged liver. No free peritoneal fluid was seen, and there was good gastrointestinal motility. Significant abnormalities were identified on CBC and biochemistry (Table 1).
Main findings on CBC and biochemistry from a 1-month-old foal that was dull and had diarrhea and seizures.
| CBC | Patient | Reference | Biochemistry | Patient | Reference |
|---|---|---|---|---|---|
| Plasma protein (g/dL) | 6.8 | 6.0–8.0 | Triglycerides (mg/dL) | 241 | 20–70 |
| Fibrinogen (mg/dL) | 800 | 100–400 | Glucose (mg/dL) | 62 | 70–135 |
| Hct (%) | 49 | 31–47 | Total protein (g/dL) | 5.8 | 5.8–7.4 |
| Platelets (X 103/µL) | 117 | 125–300 | Albumin (g/dL) | 2.3 | 2.9–3.7 |
| WBCs (X 103/µL) | 2.6 | 5.5–10.5 | Creatine kinase (IU/L) | 58,370 | 100–470 |
| Band neuts (X 103/µL) | 0.4 | 0–0.1 | Total bilirubin (mg/dL) | 3.3 | 0.3–1.8 |
| Seg neuts (X 103/µL) | 0.1 | 3–7 | AST (IU/L) | 1,593 | 185–374 |
| Lymphocytes (X 103/µL) | 1.9 | 1.5–4.0 | SDH (IU/L) | 223 | 0–10 |
| Monocytes (X 103/µL) | 0.2 | 0–0.6 | GGT (IU/L) | 54 | 10–25 |
| Bile acids (µmol/L) | 12 | < 10 | |||
| Sodium (mEQ/L) | 123 | 132–142 | |||
| Chloride (mEQ/L) | 84.4 | 97–104 | |||
| Bicarbonate (mEQ/L) | 20.0 | 26–33 |
Notes: no platelet clumping, marked toxic neutrophils, moderate reactive lymphocytes.
neuts = Neutrophils. SDH = Sorbitol dehydrogenase. seg = Segmented. T-bilirubin = Total bilirubin.
The poor prognosis rendered a decision for euthanasia (pentobarbital, 50 mg/kg, IV) and postmortem examination. The liver was diffusely enlarged and mottled pale red to dark purple (Figure 1), with disseminated pinpoint to approximately 1-mm-diameter pale-tan foci scattered throughout all lobes. The wall of the right dorsal colon was moderately thickened by edema, and the mucosa was regionally extensively dark purple. The right dorsal colon contained a moderate amount of opaque, homogeneous, bright-yellow, watery digesta. The lungs were slightly wet, heavy, and mottled pale pink to dark red.
Gross postmortem examination of a foal that was dull and had diarrhea and seizures. A—Diffusely enlarged and mottled pale-red to dark-purple liver. B—Disseminated pinpoint to approximately 1-mm-diameter pale-tan foci scattered throughout the parenchyma of all liver lobes. C—The right dorsal colon is thickened by edema, and the mucosa is dark purple. It contains a moderate amount of opaque, homogeneous, bright-yellow, watery digesta.
Citation: Journal of the American Veterinary Medical Association 263, 3; 10.2460/javma.24.09.0599
Histopathologic and Microbiological Findings
Microscopically, approximately 80% of the hepatic parenchyma had random, multifocal, approximately 1-mm-diameter foci of lytic necrosis characterized by fibrin, cellular debris, degenerate neutrophils, and hypereosinophilic shrunken necrotic hepatocytes. Peripheral to these regions, less affected hepatocytes occasionally contained numerous intracytoplasmic, stacked, pale, basophilic, elongate bacilli (Figure 2). These bacilli were argyrophilic with a Steiner stain. Additionally, there was a mild to moderate necrotizing lymphohistiocytic colitis and mild patchy gray matter edema with proliferation of Alzheimer type II astrocytes in the brain. Feces were quantitative PCR negative for equine coronavirus, equine rotavirus, Lawsonia intracellularis, Salmonella spp, Cryptosporidium spp, Rhodococcus equi, Clostridium difficile toxins A and B, and Clostridium perfringens (antigen and toxins CPA, CPB, CPB2, netF, and CPE).
Histopathology of the liver of the animal described in Figure 1. A—Multifocal, approximately 1-mm-diameter foci of lytic necrosis characterized by fibrin, cellular debris, degenerate neutrophils, and hypereosinophilic shrunken necrotic hepatocytes. Peripheral to these regions, less affected hepatocytes occasionally contain numerous intracytoplasmic, stacked, pale, basophilic, elongate bacilli. H&E stain; bar = 100 µm. B—Similar lesions shown at higher magnification. H&E stain; bar = 50 µm. C—The highlighted blue circles indicate the numerous, stacked, argyrophilic elongate bacilli within hepatocytes at the periphery of necrotic foci. Steiner stain; bar = 20 µm.
Citation: Journal of the American Veterinary Medical Association 263, 3; 10.2460/javma.24.09.0599
Diagnosis and Case Summary
Signalment, history, clinical signs, and laboratory abnormalities raised suspicion for disease caused by Clostridium piliforme, also known as Tyzzer disease, and this was subsequently confirmed at the postmortem examination. Fresh liver tissue was PCR positive for C piliforme. The leukopenia, profound neutropenia with degenerative left shift, hypoalbuminemia, and electrolyte derangements were consistent with severe acute colitis and systemic inflammatory response syndrome in equids. Hyperfibrinogenemia, hypoglycemia, and marked elevations of liver enzymes and muscle enzymes are unusual in acute equine colitis. Significant hyperfibrinogenemia is likely secondary to activation of the coagulation cascade that occurs with severe liver disease. Sorbitol dehydrogenase and GGT are liver-specific enzymes that are elevated with hepatocellular and biliary damage, respectively. Moreover, bile acid elevation, hypoglycemia, and hypoalbuminemia are consistent with compromised liver function. While elevation of AST is seen in hepatocellular disease, it is not a tissue-specific enzyme and elevation is also seen in muscle disease. Mild to moderate elevation of creatine kinase occurs with skeletal muscle damage in horses with colic; however, the more significant elevation of creatine kinase seen in this foal was likely caused by skeletal muscle damage associated with seizures. The neurologic signs seen in this foal were explained by metabolic derangements and hepatic encephalopathy. Acute onset of severe disease affecting the liver, gastrointestinal tract, and CNS was highly suspicious for Tyzzer disease.1,2 A previous report2 demonstrated that farms can have > 1 case of Tyzzer disease, with 1 farm producing as many as 24 cases. Additionally, this foal’s pasture environment contained a stream, allowing for introduction of muskrats, other rodents, and lagomorphs, which are all known carriers of C piliforme.2 Increased risk for disease development has been identified in foals born out of visiting mares versus resident mares and in foals born out of young mares (< 6 years), suggesting an important role for protection through high-quality colostrum.3
Although Tyzzer disease can lead to peracute death and is often deadly even when treatment is attempted, a good outcome of early-diagnosed disease has been reported.4 In this case, postmortem examination confirmed lesions affecting the liver, gastrointestinal tract, and brain, similar to what has been previously reported.1 Long rod-shaped bacteria found in the liver of a foal, and specifically the haystack formation within hepatocytes, are morphologic features that increase the likelihood of diagnosing C piliforme.5 Steiner silver stain was used to confirm identification of C piliforme, since this organism is uniquely argyrophilic.5 Polymerase chain reaction testing in conjunction with the histologic findings described provided strong evidence to definitively diagnose C piliforme infection.
In conclusion, while Tyzzer disease is uncommon, many factors identified in this foal’s examination led to its presumptive diagnosis. Postmortem examination, histopathological findings, and PCR confirmed the diagnosis.
Comments
Tyzzer disease is a multisystemic syndrome caused by C piliforme, affecting foals < 45 days of age.1 Transmission is orofecal, through coprophagy, a behavior appreciated in foals 2 to 5 weeks of age, at the same time Tyzzer disease occurs.2 Pasture contamination with C piliforme spores is a source of inoculation for mares,2 and while adult horses are resistant to infection, they pass spores in feces.2 Spores are highly resistant and remain in the environment for prolonged periods of time. Rapid dietary changes, high-protein diets, and consumption of fresh pasture grasses following heavy rainfall have all been associated with disease development in foals.2 Spores germinate and C piliforme colonize the intestines, causing local tissue destruction, colitis, and diarrhea. Bacteria are absorbed from the intestinal tract and enter the liver through portal circulation. Rapid hepatic colonization leads to hepatic necrosis, the classic finding in Tyzzer disease. A triad of necroinflammatory lesions that affect the liver, colon, and heart secondary to bacteremia has been reported.1 Pathophysiological processes that led to tissue destruction in this case included tissue necrosis (liver, colon), electrolyte and oncotic pressure derangements (lungs, brain), inflammatory mediators, and elevation of ammonia (brain).
Acknowledgments
None reported.
Disclosures
The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.
Funding
The authors have nothing to disclose.
ORCID
Y. S. Nout-Lomas https://orcid.org/0000-0001-6583-2308
References
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Fosgate GT, Hird DW, Read DH, Walker RL. Risk factors for Clostridium piliforme infection in foals. J Am Vet Med Assoc. 2002;220(6):785-790. doi:10.2460/javma.2002.220.785
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Borchers A, Magdesian KG, Halland S, Pusterla N, Wilson WD. Successful treatment and polymerase chain reaction (PCR) confirmation of Tyzzer’s disease in a foal and clinical and pathologic characteristics of 6 additional foals (1986-2005). J Vet Intern Med. 2006;20(5):1212-1218. doi:10.1111/j.1939-1676.2006.tb00725.x
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Fingerhood S, Mendonça FS, Uzal FA, et al. Tyzzer disease in 19 preweaned orphaned kittens. J Vet Diagn Invest. 2023;35(2):212-216. doi:10.1177/10406387231154554
