History

A 23-year-old 441-kg Quarter Horse gelding was presented due to several weeks of weight loss, intermittent hematuria, polyuria, and polydipsia. The horse also had a history of equine recurrent uveitis of the right eye and gradually lost vision in this eye over several months.

Clinical and Gross Findings

At presentation, the gelding was clinically normal except for uveitis of the right eye and hematuria. A CBC was unremarkable. A plasma biochemical profile revealed azotemia and decreased GFR (increased BUN, 34 mg/dL; reference interval [RI], 12 to 26 mg/dL; increased creatinine, 2.20 mg/dL; RI, 1.20 to 2.00 mg/dL; hypercalcemia, 17.4 mg/dL; RI, 11.3 to 13.4 mg/dL; hypermagnesemia, 2.8 mg/dL; RI, 1.7 to 2.4 mg/dL) and hypophosphatemia (1.6 mg/dL; RI, 2.7 to 5.0 mg/dL). On the basis of these findings and the measured urine specific gravity of 1.013, chronic renal disease was suspected, potentially with an acute component given concurrent finding of hyperkalemia (6.1 mmol/L; RI, 3.0 to 5.0 mmol/L). The patient also had hyperproteinemia (9.4 g/dL; RI, 6.1 to 8.1 g/dL) with hyperglobulinemia (6.2 g/dL; RI, 2.5 to 5.0 g/dL), suggestive of inflammation or potentially dehydration, and hyponatremia (129 mmol/dL; RI, 130 to 140 mmol/dL) and hypochloremia (92 mmol/dL; RI, 97 to 105 mmol/dL) attributed to renal or gastrointestinal loss.

Transabdominal and transrectal ultrasonography revealed an enlarged left kidney and enlarged mass adjacent to the kidney that was presumed to be the left adrenal gland. A cystoscopy was then performed. Unilateral hematuria was identified from the left ureter, and the ureter was catheterized for urinalysis and other diagnostic tests. A stained cytocentrifuged preparation of this urine sample revealed acute and chronic hemorrhage, based on the findings of erythrophagocytic macrophages and hemosiderophages. A urine PCR for Leptospira was negative. Intravenous fluids and antibiotics were initiated; however, due to the lack of response to therapy and poor prognosis, the horse was euthanized.

At necropsy, the kidneys were bilaterally enlarged and had numerous, coalescing, firm, well-demarcated, tan masses ranging from 1 X 0.5 cm to 8 X 8 cm (Figure 1). These masses, which predominated within the renal medulla, replaced approximately 40% of the parenchyma in the left kidney and approximately 10% of the parenchyma in the right kidney. Some of the masses had variably sized cystic cavitated areas containing red translucent fluid and soft green debris. The left adrenal glandular cortex and medulla were markedly expanded by several irregularly marginated, multilobulated, tan to yellow, firm, coalescing masses that ranged from 0.4 X 0.4 cm to 5 X 1.5 cm. The urinary bladder contained turbid and slightly red-tinged urine. The vitreous of the right eye was opaque yellow to green, and the posterior uveal tract was thickened by a thick white band.

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Postmortem image of the left kidney from a 23-year-old gelding Quarter Horse. The kidney was enlarged and had numerous, coalescing, firm, well-demarcated, tan masses in the parenchyma.

Citation: Journal of the American Veterinary Medical Association 261, 3; 10.2460/javma.22.10.0453

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Formulate differential diagnoses, then continue reading.

Cytologic and Histopathologic Findings

An impression smear of a renal mass revealed multiple renal tubular epithelial cells with low numbers of macrophages, few larvated ova, and rare nematodes exhibiting a rhabditiform esophagus and a tapered tail. Histologically, the sections representing the grossly most severely affected areas of the kidneys had up to 80% of the cortex and medulla replaced by multifocal to coalescing granulomas composed of epithelioid macrophages and multinucleated giant cells, moderate numbers of lymphocytes and plasma cells, and fewer eosinophils with numerous intralesional adult and larval nematodes and nematode eggs (Figure 2). The adult nematodes were 10 to 15 µm in diameter and had a 1-µm-thick, smooth cuticle; platymyarian musculature; a rhabditiform esophagus featured by a corpus, isthmus, and bulb; intestine lined by uninucleated cells; a dorsiflexed uterus that occasionally contained a 10 X 30-µm uninucleated egg; and a tapered tail (Figure 3). The larval nematodes were 8 to 10 µm in diameter and had the same main characteristics, including a rhabditiform esophagus and tapered tail in addition to internal basophilic granular structures. The eggs were 15 X 35 µm with a thin shell and were either morulated or larvated. These morphological features of the adult and larval nematodes and eggs were consistent with Halicephalobus gingivalis.

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Granulomatous nephritis. Infiltration of mixed inflammatory cells, including epithelioid macrophages, multinucleated giant cells, lymphocytes, and eosinophils, around several nematodes (arrows) and eggs (arrowhead). H&E stain; bar = 50 µm.

Citation: Journal of the American Veterinary Medical Association 261, 3; 10.2460/javma.22.10.0453

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Higher magnification of the intralesional nematodes. A—Nematode with rhabditid esophagus including corpus (arrow), isthmus, and bulb (arrowhead). B—Adult female nematode parasites also possess a dorsoflexed ovary (arrow) and egg (arrowhead). These features are characteristic of Halicephalobus gingivalis. H&E stain; bar = 20 µm.

Citation: Journal of the American Veterinary Medical Association 261, 3; 10.2460/javma.22.10.0453

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The lesions in the left adrenal gland, lumbar lymph node, and right eye were similar to those in the kidneys. The lesions consisted of multifocal to coalescing granulomatous inflammation with intralesional adult and larval rhabditid nematodes and eggs.

Morphologic Diagnoses and Case Summary

Kidneys, adrenal gland, lumbar lymph node, and right eye: inflammation, granulomatous and eosinophilic, multifocal to coalescing, chronic, with intralesional adult and larval rhabditid nematodes and eggs.

Case summary: granulomatous and eosinophilic nephritis, adrenalitis, lumbar lymphadenitis, and right posterior uveitis associated with H gingivalis infection.

Comments

H gingivalis (formerly Micronema deletrix or Halicephalobus deletrix) is a free-living, saprophytic, rhabditid nematode that inhabits the soil and organic matter.¹ The parasite has a worldwide distribution, but the infection is rare and sporadic. The parasitic disease is most commonly reported in horses, especially in North America and Europe, but it has also been documented in humans, donkeys, zebras, and dairy cattle.¹ Although the pathogenesis, life cycle, and route of infection are poorly understood, H gingivalis is thought to infect through wounds in the mouth or skin.¹ While no significant wounds were evident in this case, the gelding was a companion to recently weaned younger horses and minor wounds may have occurred as social dynamics were established. The most commonly affected organs in the horse are the brain, spinal cord, and kidneys. Other organs such as the eyes, lymph nodes, heart, lungs, stomach, peripheral nerve ganglia, and liver can also be involved.¹

Clinical signs associated with H gingivalis infection vary depending on the location and severity of the lesions. In horses, neurological signs are most common, often in combination with renal dysfunction.¹ In addition, when H gingivalis infects the eye, it can cause blindness associated with granulomatous anterior uveitis, chorioretinitis, and/or optic neuritis.² In our gelding, the clinically diagnosed uveitis in the right eye was similarly the result of chronic H gingivalis infection, with no histological evidence of equine recurrent uveitis.

CBC and serum biochemistry may reveal the presence of anemia, azotemia, hyperproteinemia, and hyperglobulinemia.³ These abnormalities, while not specific to H gingivalis infection, are attributable to renal dysfunction, decreased production of erythropoietin, hemorrhage from the affected kidneys, and chronic inflammation.^3,4

The ultrasonographic findings of unilateral renal and adrenal enlargement warranted the clinical differential diagnosis of a renal tumor. The most common primary renal tumor in horses is renal carcinoma.⁴ It is an infrequent unilateral lesion, however, with rare metastasis to the contralateral kidney and lung. Azotemia and other related biochemical abnormalities are much more common with H gingivalis infection, which can involve both kidneys and consequently more often causes renal dysfunction. H gingivalis infection should therefore be a clinical consideration in horses not only with neurologic signs, but also with evidence of renal disease and/or uveitis.

The definitive diagnosis of the infection is generally made postmortem by histologic identification of the parasites that are morphologically compatible with rhabditid nematodes.⁵ Molecular methods, such as PCR, are sometimes used for the identification of the parasite,⁵ but the diagnosis can also be made morphologically, as in this case. The parasite can rarely be detected in urine and semen,¹ and examination of centrifuged urine samples might therefore be useful as an antemortem diagnostic method in cases of kidney infection.¹ No parasites were seen on urinalysis in this case, however. A biopsy may also be an effective antemortem method to detect the parasite in the lesions, but especially in the case of horses with renal dysfunction, renal biopsy is controversial because of potential complications, such as bleeding.⁴

H gingivalis infections are highly lethal, and to our knowledge, there have been only 4 cases of successful treatment in affected horses.⁵ Two horses that survived had posthitis and were treated with ivermectin or moxidectin. In the other 2 cases, 1 donkey with unilateral nephritis and 1 horse with a mass adjacent to the left eye, nephrectomy and surgical debulking of the lesion adjacent to the eye, respectively, in combination with the administration of ivermectin, were successful in treating the animals.

Successful treatment of horses with disseminated granulomatous lesions and/or neurological signs has yet to be reported. This is thought to be due to the fact that anthelmintics do not cross the blood-brain barrier and do not penetrate the granulomatous lesions and/or that H gingivalis might not be susceptible to anthelmintics such as ivermectin or benzimidazole.^1,5 In this case, the horse had bilateral nephritis, unilateral adrenalitis, regional lymphadenitis, and unilateral posterior uveitis, suggesting treatment would likely have been unrewarding.