History

A 9-year-old 40.2-kg sexually intact male Great Pyrenees was presented to a veterinary medical teaching hospital for evaluation of regurgitation and vomiting, a severely distended abdomen, sternal recumbency, and poor body condition. The dog had been previously evaluated because of severe abdominal effusion 1 year earlier, at which time 4 L of abdominal fluid was removed.

Clinical and Clinicopathologic Findings

On physical examination, the dog was estimated to be 5% dehydrated and had pyrexia (rectal temperature, 39.6 °C). A CBC revealed borderline low hemoglobin concentration (13.9 g/dL; reference interval, 14 to 19 g/dL) with mild microcytosis (mean corpuscular volume, 62.9 fL; reference interval, 65 to 75 fL) and normal mean corpuscular hemoglobin concentration (34.6 g/dL, reference interval, 33 to 36 fL). A mild stress leukogram characterized by mild neutrophilia (13,959 cells/µL; reference interval, 3,000 to 10,500 cells/µL), lymphopenia (873 cells/µL; reference interval, 1,000 to 4,000 cells/µL), and slight monocytosis (1,549 cells/µL; reference interval, 150 to 1,200 cells/µL) was revealed. Mild thrombocytosis was also present (590,000 platelets/µL; reference interval, 150,000 to 400,000 platelets/µL). No left shift or toxic changes among neutrophils were noted during examination of a blood smear. A serum biochemical panel and venous blood gas analysis revealed severe metabolic alkalemia (blood pH, 7.545) with concurrent metabolic acidosis (anion gap, 24 mMol/L; reference interval, 12 to 20 mMol/L) as well as mild hypoalbuminemia, hypercalcemia, and hyperglycemia. The latter findings were consistent with vomiting, dehydration, and corticosteroid-mediated stress.

Abdominal ultrasonography revealed a large volume of free peritoneal fluid that was aspirated for analysis. The peritoneal fluid had a total protein concentration of 4.2 g/dL, total nucleated cell count of 7,200 cells/µL, and < 20,000 RBCs/µL. Grossly, peritoneal fluid (pre- and postcentrifugation) appeared straw-colored, milky, and flocculent; a serum sample collected at the same time appeared clear (Figure 1). A direct smear preparation of the peritoneal fluid had numerous plate-like and notched clear structures as well as many clear needle- and rod-shaped structures. Nucleated cells were primarily lipid-laden macrophages (91%) arranged singly or in small loosely cohesive clusters. Nondegenerated neutrophils (7%) and rare small lymphocytes (2%) were also seen. No infectious agents or overtly neoplastic cells were observed.

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Images of a sample of free peritoneal fluid obtained from the abdominal cavity of a 9-year-old Great Pyrenees that was evaluated because of regurgitation and vomiting, a severely distended abdomen, sternal recumbency, and poor body condition. A sample of serum was obtained at the same time. A—Photographs of the milky and opaque gross peritoneal fluid (left) and the transparent serum (right). B—Photomicrograph of direct smear preparation of the peritoneal fluid. There are many scattered negatively stained plate-like and rod-like structures (arrows) in a pink proteinaceous background, along with low numbers of foamy macrophages (arrowhead). Wright-Giemsa stain; bar = 200 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.19.06.0296

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Additional Clinicopathologic Findings

The peritoneal fluid had cholesterol and triglycerides concentrations of 338 mg/dL and 88 mg/dL, respectively, and a cholesterol-to-triglycerides concentration ratio of 3.84. The dog’s serum cholesterol concentration was 242 mg/dL (reference interval, 139 to 353 mg/dL). Because of the dog’s overall poor health and prognosis, euthanasia (by IV infusion of pentobarbital) was elected. Necropsy of the carcass was permitted. The dog was emaciated with generalized muscle loss. Approximately 5 L of thin, opaque, shiny, pink to golden brown fluid filled the abdominal cavity. Diffusely, the abdominal lining and serosa of the entire intestinal tract, liver, kidneys, and omentum were thickened by tan, firm irregular fibrosis and numerous, thick, tortuous blood vessels. On histologic examination of intestinal tissue sections, marked serosal fibrosis was confirmed; the mesothelium was mostly lost (Figure 2).

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Photograph of the opened abdominal and thoracic cavities obtained during necropsy and photomicrographs of a section of small intestinal tissue. A—Notice the peritoneal effusion with a distinct satin-like sheen, as well as marked peritoneal fibrosis extending from the abdominal wall and incorporating the small intestinal serosa as well as the capsular surface of the liver and kidney. B—In the small intestinal tissue, there is marked serosal thickening composed of fibrosis and disorganized angiogenesis. H&E stain; bar = 1,000 µm. C—In this image of the small intestinal tissue, serosal fibrosis with mesothelial lining loss is evident. H&E stain; bar = 100 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.19.06.0296

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Interpretation and Case Summary

Interpretation and case summary: severe abdominal pseudochylous effusion (PCE) with sclerosing encapsulating peritonitis (SEP) in a dog.

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Pseudochylous effusion, also known as cholesterol effusion or chyliform effusion, is characterized primarily as an effusion with high cholesterol content. Its gross appearance is typically milky (similar in appearance to chylous effusion) but inclusion of cholesterol crystals may impart a distinct satin-like sheen to the fluid (Figure 2).¹ In human medicine, PCE is defined by a high peritoneal fluid cholesterol concentration (usually > 250 mg/dL), fluid cholesterol-to-triglycerides concentration ratio > 1.0, total protein concentration > 4.0 g/dL, absence of chylomicrons, and variable presence of rhomboid-shaped cholesterol crystals (although approx 10% of affected humans may not have this finding).^2–4 In the case described in the present report, the numerous clear structures in the abdominal fluid were typical cholesterol crystals.

The amount of fluid inside a body cavity is regulated by the amount of fluid that enters the cavity and the amount that leaves the cavity. Lymphatic drainage removes accumulated fluid inside body cavities.^5,6 In veterinary medical practice, effusion formation is generally considered to involve mechanisms associated with increased fluid formation, such as increased vascular hydraulic pressure or permeability and decreased oncotic pressure. However, effusion may also be formed by decreased removal of fluid from the cavity. In the dog of the present report, SEP was present, which affected both the vascular and lymphatic systems and also compromised the mesothelium. Hence, the effusion likely accumulated as a result of increased fluid formation and altered fluid absorption and recycling.

The cholesterol-rich nature of PCE is mostly attributed to cell membrane degeneration of cell-rich fluids.³ Nevertheless, although high-cellularity exudates are very common in veterinary medicine, PCE is rarely described, suggesting the involvement of alternative or additional mechanisms in the pathogenesis of PCE. It is largely accepted that most cavitary neutrophils die within the cavity and are phagocytized and recycled by local macrophages.^7,8 The outcome events for macrophages remains a matter of some debate. For a long time, it was believed that emigration to lymph nodes was the major mechanism associated with macrophage clearance from cavitary fluids. In a recent quantitative study,⁹ it was concluded that local apoptosis has a more fundamental role in that clearance process. In a situation where the serosa becomes fibrotic or even calcified, it is likely that the normal transit of cellular components as well as fluid could be compromised, thereby leading to fluid accumulation inside the cavity.

Pseudochylous effusion is considered rare in humans, and a search of the veterinary medical literature suggested that it develops even less frequently in domestic animals. In humans, PCE has been reported primarily as a consequence of tuberculosis or rheumatoid arthritis and less frequently as a consequence of paragonimiasis, echinococcosis, hydatidosis, yellow nail syndrome, Demons-Meigs syndrome, iatrogenesis, neoplasia, or trauma.^4,10–17 Two case reports of cholesterol-rich effusions in dogs have been published but the effusions were either associated with a hemorrhagic component in a dog with concurrent marked hypercholesterolemia¹⁸ or possible inadvertent aspiration of an ovarian cyst,¹⁹ and did not meet the defining criteria of PCE. Another case of a dog with tuberculosis that had a milky opaque pleural effusion containing cholesterol crystals was reported but did not include any data regarding about cholesterol or triglycerides concentration or presence of cylomicrons.²⁰ To the author’s knowledge, no cases involving domestic species that meet all criteria for PCE have been reported to date.

It is important to distinguish PCE from chylous effusions because each type of effusion is associated with different pathophysiologic mechanisms, underlying causes, treatment approaches, and prognosis. Treatment of humans with pleural PCE may involve thoracentesis with thoracic drainage, pleurectomy, pleurodesis, and medicinal treatment and prognosis is dependent on the underlying cause. A poor or unfavorable outcome has been reported for 6.7% to 62.5% of patients with PCE, depending on the severity of their clinical condition.^4,21

For the dog of the present report, an additional diagnosis of SEP was made, and the SEP may have been associated with PCE formation. In dogs, SEP is associated with extensive fibrosis that encapsulates the abdominal organs.²² In fact, the dog of the present report was examined 1 year earlier and 4 L of abdominal fluid was removed, supporting the chronicity of effusion formation in this case. Poor body condition, as noted in this dog, often accompanies SEP. In the only reported case of SEP in a dog for which fluid triglycerides and cholesterol concentrations were measured (1,171 mg/dL and 50 mg/dL, respectively), the effusion was classified as chylous.²³

In dogs, SEP is considered a chronic and progressive disease with a very low survival rate.²⁴ The marked fibrosis of serosal surfaces may compromise lymphatic drainage of free abdominal fluid, leading to free fluid accumulation. In the dog of the present report, the fibrotic serosa also contained striking vascular remodeling as evidenced by numerous, thick, tortuous blood vessels (Figure 2). This finding may have caused fluid leakage into the abdomen; that fluid leakage, in conjunction with poor fluid reabsorption and accumulation of cellular breakdown products, may have resulted in formation of a cholesterol-rich effusion.

Reported causes of SEP in dogs include historic abdominal surgery, intra-abdominal steatitis, bacterial peritonitis, foreign body ingestion,^23,24 necrotic omental lipoma,²⁵ abnormal liver development,²⁶ mesothelioma,²⁷ hepatocellular carcinoma,²⁸ and leishmaniasis.²⁹ However, most canine cases of SEP are considered idiopathic in origin and often associated with intraperitoneal chronic inflammation. For the dog of the present report, there was no evidence of any of those causes at necropsy. Most affected dogs respond poorly to empirical treatment, and euthanasia is usually advised; however, 1 dog improved dramatically with tamoxifen treatment.²⁴

Although PCE in companion animals is rare, increased awareness and more effective diagnosis of the condition may enable the differentiation of PCE from chylous effusion in future cases. Additional studies are necessary to investigate the underlying pathogenesis of PCE, treatment options, and prognosis for affected companion animals.