Signalment:  

A 10-year-old, male, Labrador retriever. The dog had recently become ataxic, non-responsive to the owner, uncomfortable when lying down, and had watery diarrhea for several days before presentation. Radiographs revealed diffuse calcification throughout the small intestine, enlarged liver, and diffuse spondylosis of the thoracic and lumbar vertebral columns. An ultrasound revealed multiple hypoechoic nodular masses in the liver and diffuse hyperechogenicity of the submucosa of the small intestine. Because of the grave prognosis, owner elected euthanasia. Biopsy specimens of liver, spleen, and small intestine were collected.

Gross Description:  

Received for biopsy was a 10 cm segment of small intestine. The wall was firm and thickened and had multiple, 1-3 mm, white, raised foci on the serosal surface. The entire circumference of the submucosa was prominent, gritty and white. 

Morphologic Diagnosis:  

Small intestine: Enteritis, granulomatous, eosinophilic, transmural, chronic, severe, with large numbers of mineralized and unmineralized, trematode eggs (Heterobilharzia americana)

Lab Results:  

CBC and serum chemistry panel revealed anemia, elevated liver enzymes (AST, ALP, ALT, and Total bilirubin), hypoalbuminemia, hyperglobulinemia, and hypocholesterolemia.

Condition:  

Heterobilharzia americana

Contributor Comment:  

Heterobilharzia americana (Digenea: Schistosomatidae) is a blood trematode that causes canine schistosomiasis in North America. Natural H. americana infection has been reported in bobcat, armadillo, beaver, dogs, coyote, a captive born Brazilian tapir, mountain lion, mink, nutria, opossums, raccoons, red wolves, swamp rabbits, white-tailed deer, etc. Geographically the natural infection is essentially limited to the southern Atlantic Coast states (Florida, Georgia, North Carolina, South Carolina) and Gulf Coast states (Texas, Louisiana, Mississippi), although it has been reported in Kansas. 

Members of this family, Schistosomatidae, are the only trematodes that live in the blood stream of warm-blooded hosts. They are dioecious, the male bearing the female in the ventral gynaecophoric canal. There are no metacercaria. The cercariae become fork-tailed and penetrate directly through the skin of the host. In the eggs there are no opercula. The intermediate hosts are snails of the genera Fossaria cubensis (= Lymnaea cubensis) and Pseudosuccinea columella. The adult worms reside in the mesenteric veins. The eggs laid in the mesenteric veins produce enzymes to erode through submucosa and mucosa of the intestine to reach the intestinal lumen. Some of the eggs are carried by the venous flow to the liver, spleen, and other organs such as the lungs and brain. Once the eggs containing mature miracidia leave the host, they must reach water of low osmotic pressure in order to hatch. The miracidia swim actively until they find snails of the right species. They bore into them and become mother sporocysts that produce daughter sporocysts that in turn produce cercariae. A single miracidium can produce several thousand cercariae. They leave the snail, swim in the water, and enter the host by penetrating through the skin and into the lymphatics. 

Clinical signs of canine H. americana infection include dermatitis due to skin penetration, coughing, chronic intermittent mucoid to hemorrhagic diarrhea, and anorexia. Significant clinical pathology findings include anemia, hyperglobulinemia, hypoalbuminenia, eosinophilia, and hypercalcemia in some cases. No hypercalcemia or eosinophilia was noted in this particular case, however. Although the pathogenesis of hypercalcemia in schistosomiasis is not fully understood, a recent report described hypercalcemia with elevated parathyroid hormone-related protein (PTHrP) in canine schistosomiasis. Fecal floatation is usually ineffective in the diagnosis of H. americana infection. Saline sedimentation or a miracidia hatch is necessary to diagnose the infection. Incidentally, the liver (not submitted) of the current case had eosinophilic granulomatous hepatitis with numerous intralesional trematode eggs.

JPC Diagnosis:  

Small intestine: Enteritis, granulomatous, submucosal, circumferential, multifocal to coalescing and multifocally transmural, severe, with myriad schistosome eggs, Labrador retriever (Canis familiaris), canine.

Conference Comment:  

Heterobilharzia americana and Schistomatium douthitti are the two species of schistosomes that infect mammals in the United States of America.⁷ Although typically limited to the southern Atlantic and Gulf of Mexico coastal states, H. americana infection in Kansas has been reported, presumably linked to the importation of infected raccoons into the state during the mid-20th century.⁷

The most tissue damage occurs during oviposition and extrusion of the eggs through the tissue. The ideal movement of eggs to the outside world includes penetration of the mesenteric vessels, lamina propria and exit into the intestinal lumen, through secretions produced by the miracidium as well as through mechanical disruption.⁶ When the eggs migrate in the wrong direction or get swept into the portal or systemic circulation, they can induce a granulomatous reaction in a variety of organs (lymph node, liver, lungs, etc.), depending on where they lodge.⁶

The eggs within tissue usually invoke a hypersensitivity reaction, resulting in a granulomatous response that is followed by degeneration or mineralization of the schistosome eggs and eventual fibrosis.⁶ The mineralization of the schistosome eggs in this case is unusual in its extent. 

Although hypercalcemia was not seen in this case, it has been associated with chronic granulomatous inflammation.⁸ Activated macrophages produce calcitriol that is not regulated by parathyroid hormone, calcitriol, or calcium levels.⁸ Causes of hypercalcemia are listed below:

• Neoplasia (lymphoma, multiple myeloma, adenocarcinoma of the apocrine gland of the anal sac, tumors metastatic to bone)
• Primary hyperparathyroidism (hyperplasia, adenoma, adenocarcinoma) - elevated levels of circulating parathormone cause increased intestinal absorption of calcium and phosphorus as well as increased renal activation of vitamin D
• Granulomatous inflammation (canine blastomycosis, bovine paratuberculosis, schistosomiasis)
• Hypoadrenocorticism (increased tubular resorption of calcium)
• Osteolytic lesions of bone
• Immobilization
• Metabolic acidosis
• Renal failure in horses (rarely canine renal failure associated with familial disease)

References:

1. Cullen JM: Liver, biliary system, and exocrine pancreas. In: Pathologic Basis of Veterinary Disease, eds. McGavin MD, Zachary JF, 4th ed., pp. 437-439. Elsevier, St. Louis, MO, 2007
2. Fradkin JM, Braniecki AM, Craig TM, Ramiro-Ibanez F, Rogers KS, Zoran DL: Elevated parathyroid hormone-related protein and hypercalcemia in two dogs with schistosomiasis. J Am Anim Hosp Assoc 37:349-355, 2001
3. Goff WL, Ronald NC: Certain aspects of the biology and life cycle of Heterobilharzia americana in East Central Texas. Am J Vet Res 42:1775-1777, 1981
4. Krotoski WA, Job CK, Cogswell FB, Malek EA: Enzootic schistosomiasis in a Louisiana armadillo. Am J Trop Med Hyg 33:269-272, 1984
5. Malek EA, Short RB, Teehan WH, Jama A: Differential susceptibility of snail hosts to Heterobilharzia americana from Texas and Louisiana. J Parasit, 73:872-873, 1987
6. Maxie MG, Robinson WF: Cardiovascular system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., vol. 3, pp. 95-97. Elsevier Limited, St. Louis, MO, 2007
7. McKown RD, Veatch JK, Fox LB: New locality record for Heterobilharzia americana. J Wildl Dis 27:156-160, 1991 8. Rohrer CR, Phillips LA, Ford SL, Ginn PE: Hypercalcemia in a dog: a challenging case. J Am Anim Hosp Assoc 36:20-25, 2000

A virtual slide is not available for this case.

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