• View in gallery

    Postmortem photograph of the hemisected left eye (after 24-hour fixation in neutral-buffered 10% formalin) of a 4-year-old, 2.8-kg castrated male domestic shorthair cat that had a hunched stance, inappetence, reluctance to walk, and eventual lateral recumbency. Abundant semisolid translucent exudate fills the anterior, posterior, and vitreous chambers.

  • View in gallery

    Photomicrographs of the eye in Figure 1. A—The vitreous chamber has abundant serous protein and fibrin exudate (asterisk). H&E stain; bar = 5 mm. B and C—Abundant lymphocytes, plasma cells, Mott cells (arrows), rare neutrophils, and macrophages are in the exudate as well as infiltrating and expanding the iris, ciliary body, retina, and choroid. H&E stain; bar = 50 µm (B) and 25 µm (C), respectively. B inset—Macrophages show strong cytoplasmic immunostaining. Immunohistochemical staining with anti-feline infectious peritonitis virus monoclonal antibody; bar = 25 µm. D—There is retinal detachment (asterisk). H&E stain; bar = 500 µm. Inset—Hypertrophied and individualized retinal pigment epithelial cells (tombstone cells) are evident. H&E stain; bar = 25 µm.

  • 1.

    Townsend WM. Veterinary clinics small animal practice: canine and feline uveitis. Vet Clin Small Anim. 2008;38:323346.

  • 2.

    Colitz CMH. Feline uveitis: diagnosis and treatment. Clin Tech Small Anim Pract. 2005;20:117120.

  • 3.

    Andrew SE. Feline infectious peritonitis. Vet Clin North Am Small Anim Pract. 2000;30:9871000.

  • 4.

    Rohrbach BW, Legendre AM, Baldwin CA. Epidemiology of feline infectious peritonitis among cats examined at veterinary medical teaching hospitals. J Am Vet Med Assoc. 2001;218:11111115.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Hartmann K, Binder C, Hirschberger J, et al. Comparison of different tests to diagnose feline infectious peritonitis. J Vet Intern Med. 2003;17:781790.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Pesteanu-Somogyi LD, Radzai C, Pressler BM. Prevalence of feline infectious peritonitis in specific cat breeds. J Feline Med Surg. 2006;8:15.

  • 7.

    Worthing KA, Wigney DI, Dhand NK, et al. Risk factors for feline infectious peritonitis in Australia. J Feline Med Surg. 2012;14:405412.

  • 8.

    Foley JE, Poland A, Carlson J, Pedersen NC. Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus. J Am Vet Med Assoc. 1997;210:13131318.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Norris JM, Bosward KL, White JD, Baral RM, Catt MJ, Malik R. Clinicopathological findings associated with feline infectious peritonitis in Sydney, Australia: 42 cases (1990–2002). Aust Vet J. 2005;83:666673.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Grahn B, Peiffer G, Wilcock B. Histologic manifestations of disorders of the uvea. In: Grahn B, ed. Histologic Basis of Ocular Cisease. 1st ed. John Wiley & Sons, Inc; 2019:197253.

    • Search Google Scholar
    • Export Citation
  • 11.

    Rissi DR. A retrospective study of the neuropathology and diagnosis of naturally occurring feline infectious peritonitis. J Vet Diagn Invest. 2018;30(3):392399.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Addie D, Belák S, Boucraut-Baralon C, et al. Feline infectious peritonitis. ABCD guidelines on prevention and management. J Feline Med Surg. 2009;11:594604.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Boettcher IC, Matiasek K, Greene CE, Hartmann K, Fischer A. Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats. J Am Vet Med Assoc. 2007;230:199205.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Giori L, Giudice C, Grieco V, Paltrinieri S. Performances of different diagnostic tests for feline infectious peritonitis in challenging clinical cases. J Small Anim Pract. 2011;52:152157.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Kipar A, Meli ML. Feline infectious peritonitis: still an enigma? Vet Pathol. 2014;51:505526.

  • 16.

    Goodson T, Randell S, Moore L. Feline infectious peritonitis. Compend Contin Educ Vet. 2009;31:E18.

  • 17.

    Foley JE, Leutenegger C. A review of coronavirus infection in the central nervous system of cats and mice. J Vet Intern Med. 2001;15:438444.

  • 18.

    Foley JE, Rand C, Leutenegger C. Inflammation and changes in cytokine levels in neurological feline infectious peritonitis. J Feline Med Surg. 2003;5:313322.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Felten S, Hartmann K. Diagnosis of feline infectious peritonitis: a review of the current literature. Viruses. 2019;11(11):135.

Advertisement

Pathology in Practice

View More View Less
  • 1 Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL
  • | 2 Louisiana Animal Disease Diagnostic Laboratory, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA
  • | 3 Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

Abstract

In collaboration with the American College of Veterinary Pathologists

History

A 4-year-old 2.8-kg castrated male domestic shorthair cat was evaluated because of a 1-month history of bilateral ocular opacity and a 3-day history of hunched stance in the hind limbs, reluctance to walk, inappetence, and eventual lateral recumbency. The cat had outdoor access and lived in a rural area. Empirical treatment with prednisone drops (0.2 mg/kg, PO, q 12 h) was instituted before any veterinary evaluation.

Clinical and Gross Findings

On physical examination, the cat showed signs of discomfort with any movement of the vertebral column and neck. The cat was quiet, alert, responsive, tachypneic (56 breaths/min; reference interval, 16 to 40 breaths/min), hypothermic (37.55 °C; reference interval, 38 to 39.5 °C), and had a femoral pulse of 160 beats/min.

A CBC and a serum biochemical profile were performed. Hematologic analysis revealed mild regenerative anemia (6.39 X 106 RBCs/µL [reference interval, 7.40 X 106 to 0.60 X 106 RBCs/µL]; hemoglobin concentration, 11.5 g/dL [reference interval, 12.0 to 15.5 g/dL]; and RBC distribution width, 14.3% [reference interval, 14.5% to 18.1%]), lymphopenia (0.7 X 103 cells/µL; reference interval, 1.5 X 103 to 7.0 X 103 cells/µL), and hyperproteinemia (8.5 g/dL; reference interval, 6.0 to 7.5 g/dL). Serum biochemical abnormalities included hyperglycemia (126 mg/dL; reference interval, 77 to 96 mg/dL), low activities of alkaline phosphatase (18 U/L; reference interval, 33 to 72 U/L) and creatine kinase (12 U/L; reference interval, 266 to 419 U/L), and low concentrations of BUN (12 mg/dL; reference interval, 16 to 22 mg/dL) and creatinine (1.2 mg/dL; reference interval, 1.7 to 1.9 mg/dL). Electrolyte disorders include hypercalcemia (10 mg/dL; reference interval, 8.8 to 9.3 mg/dL), hypokalemia (3.8 mmol/L; reference interval, 4.0 to 5.0 mmol/L), and hypochloremia (114 mmol/L; reference interval, 121 to 126 mmol/L). The concentration of total proteins was slightly high (7.7 g/dL; reference interval, 6.5 to 7.1 g/dL) due to hyperglobulinemia (4.8 g/dL; reference interval, 3.7 to 4.1 g/dL).

Ophthalmologic examination revealed severe bilateral lens opacity, anterior uveitis, vertical nystagmus, and partial retinal detachment. Palpebral reflex was absent in the left eye, which also had mild nystagmus. The cat tested negative for FIV and FeLV. Given the severity of the clinical signs, the patient's prognosis was considered poor, and euthanasia was elected.

Gross postmortem examination of both globes revealed that the external adnexal structures were within clinically normal limits. Hemisection of both globes after 24-hour fixation in neutral-buffered 10% formalin revealed abundant amounts of semisolid translucent exudate filling the anterior, posterior, and vitreous chambers (Figure 1). No other clinically meaningful alterations were grossly appreciated at necropsy.

Figure 1
Figure 1

Postmortem photograph of the hemisected left eye (after 24-hour fixation in neutral-buffered 10% formalin) of a 4-year-old, 2.8-kg castrated male domestic shorthair cat that had a hunched stance, inappetence, reluctance to walk, and eventual lateral recumbency. Abundant semisolid translucent exudate fills the anterior, posterior, and vitreous chambers.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.04.0201

Formulate differential diagnoses, then continue reading.

Histopathologic and additional Clinicopathologic Findings

Multiple tissue samples were collected from the CNS, eye, gastrointestinal tract, lymph nodes (pancreatic, mesenteric), lung, bone marrow, heart, liver, kidneys, spleen, sciatic nerves, skeletal muscles, adrenal glands, and pancreas. Tissue samples were fixed in neutral-buffered 10% formalin and routinely processed for histologic examination.

Histologically, the anterior, posterior, and vitreous chambers of both eyes, more severely affecting the left eye, were filled by homogenous eosinophilic material mixed with fibrin exudate embedding numerous lymphocytes, plasma cells, Mott cells, and rare neutrophils and macrophages (Figure 2). Occasional macrophages had strong cytoplasmic immunoreactivity against anti-feline infectious peritonitis (FIP) virus monoclonal antibody. Similar cellular infiltrates expanded the iris, ciliary body, retina, and choroid as well as frequently surrounded the small and mid size choroidal vessels, which had acellular, hyalinized vessel walls. Retinal detachment and mild corneal vascularization with associated few scant degenerating and viable neutrophils were also appreciated.

Figure 2
Figure 2

Photomicrographs of the eye in Figure 1. A—The vitreous chamber has abundant serous protein and fibrin exudate (asterisk). H&E stain; bar = 5 mm. B and C—Abundant lymphocytes, plasma cells, Mott cells (arrows), rare neutrophils, and macrophages are in the exudate as well as infiltrating and expanding the iris, ciliary body, retina, and choroid. H&E stain; bar = 50 µm (B) and 25 µm (C), respectively. B inset—Macrophages show strong cytoplasmic immunostaining. Immunohistochemical staining with anti-feline infectious peritonitis virus monoclonal antibody; bar = 25 µm. D—There is retinal detachment (asterisk). H&E stain; bar = 500 µm. Inset—Hypertrophied and individualized retinal pigment epithelial cells (tombstone cells) are evident. H&E stain; bar = 25 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.04.0201

The meninges and neuroparenchyma of the cerebrum, cerebellum, brainstem, spinal cord (cervical, thoracic, lumbar, and sacral segments), and choroid plexus were markedly expanded and infiltrated by large numbers of lymphocytes, plasma cells, Gitter cells, lesser numbers of Mott cells, and rare neutrophils mixed with edema, fibrin exudate, and cellular debris. Meningeal and parenchymal vessels had severe perivascular cuffing predominately composed of similar mononuclear cellular infiltrate. Within several segments of the spinal cord, moderate dilation of myelin sheaths, axonal swelling with the formation of spheroids, and multiple digestion chambers containing axonophages and axonal fragments were seen. Results were negative for direct fluorescent antibody examinations against rabies virus and FIP virus performed on fresh cerebral tissue.

Morphologic Diagnosis and Case Summary

Morphologic diagnoses:

Eye, bilateral: pyogranulomatous and lymphoplasmacytic panuveitis and perivasculitis, lymphoplasmacytic, chronic diffuse, severe with serofibrinous exudation and retinal detachment.

Central nervous system: meningoencephalomyelitis, ventriculitis, choroid plexitis, pyogranulomatous and lymphoplasmacytic, chronic, diffuse, severe.

Case summary: ocular and neurologic FIP in a cat.

Comments

In this case, the history combined with the clinical, histologic, and immunohistochemical examination findings confirmed a diagnosis of FIP with severe ocular and neurologic clinical manifestation. All the remaining visceral organs were not affected. Several etiologies, including hereditary factors, lens-associated inflammation, trauma, systemic disease, exposure to infectious organisms, or the presence of neoplasia, alone or in combination, can cause uveitis.1,2 In cats, the infectious agents to be considered are viral (FeLV, FIV, FIP virus, and feline herpesvirus), protozoal (Toxoplasma gondii), bacterial (Bartonella spp), and fungal (Cryptococcus spp, Coccidioides spp, Aspergillus spp, Blastomyces spp, and Histoplasma spp) microorganisms.1,2

Feline infectious peritonitis is caused by a virulent biotype of mutated feline coronavirus that is considered a relatively common, incurable, and fatal disease.35 Feline coronavirus is limited to the gastrointestinal tract, but some virulent mutated strains can replicate within the macrophages.3 The route of transmission for this virus is fecal-oral.3 Feline infectious peritonitis is a major cause of death in young adult cats, especially if housed with other cats, as is the case in purebred catteries and shelters. The majority of the affected cats develop the disease between 3 months to 3 years of age; however, FIP can occur at any age. Male and sexually intact cats are predisposed.4,69 The disease has no breed predisposition but pure breeds, such as Bengals, Burmese, British Shorthair, and Himalayans, are occasionally reported as being more susceptible.4,69 Some authors6 speculate that the incidence of FIP in purebred varieties is related to the concentration of inherited factors through in-breeding.

Three main disease presentations of FIP are the effusive form (wet), the noneffusive form (dry), and the neuro-ocular form.35 If a cat has a strong cell-mediated immune response, the virus can be eliminated from the system without causing disease.3 However, if a cat cannot mount an appropriate cell-mediated immune response to the virus, disseminated infection develops.35 The wet form occurs due to type III hypersensitivity,3 and the dry form is secondary to type IV hypersensitivity with partial cell-mediated immunity and classic granuloma formation.3 The effusive form is characterized by an accumulation of high protein exudates in the thorax, abdomen, or both, which typically contain a low number of cells,35 whereas the noneffusive form is characterized by pyogranulomatous to granulomatous inflammation affecting multiple organs, but especially mesenteric lymph nodes, kidney, liver, lung, brain, and eye.35 Solitary or multifocal granulomas in the gastrointestinal tract can develop too, especially in the ileocecal junction.4,69 The neuro-ocular form of FIP is seen in the absence of other systemic manifestations or combination with dry form FIP. Neurologic involvement can occur with the ocular disease as described in this case.35

The clinical signs observed with the neuro-ocular form of FIP always are seen affecting both eyes.10 Large keratic precipitates, scleral and orbital involvement, retinal detachment, optic neuritis, and anterior uveitis are reported.10 The histological lesions are variable and nonspecific, contrasting with the classical emphasis in “pyogranulomatous panuveitis” associated with FIP in the dry form.10 Inflammatory aggregates in the ocular chambers and the uveal tract can be composed of neutrophils, lymphocytes, macrophages, and plasma cells mixed with fibrin exudate.10 The early lesions of FIP (dry and neuro-ocular forms) in tissues are characterized by destructive neutrophilic and fibrinous disease, whereas, in chronic cases, granulomatous and lymphocytic inflammation is seen.10 Anecdotally, the most iconic histologic lesion is the necrotizing fibrinoid vasculitis of the small-caliber vessels surrounded by a mixed neutrophilic to granulomatous vasculitis; however, this is considered uncommon in ocular lesions.10 Therefore, the lack of this feature cannot completely rule out FIP.4

Lesions of the central nervous system associated with FIP usually target the leptomeninges, ventricles, choroid plexus, and neuroparenchyma,11 as we described in the case herein. Typical distribution of neurologic lesions includes periventricular encephalitis, rhombencephalitis, diffuse leptomeningitis, and superficial encephalitis.11

High variable histological lesions can be appreciated, and therefore, the final diagnosis can become somewhat challenging. Accurate history information, CBC, serum biochemical profile, effusion, or cerebrospinal fluid analysis, in combination with direct or indirect viral detection, should be performed.12,13 Hematologic findings include anemia, hyperproteinemia, hyperglobulinemia, neutrophilic leukocytosis, and lymphopenia.12,14

Antemortem available laboratory tests include antibody detection in blood and effusions as well as direct viral antigen detection through fluorescent antibodies of effusion or tissues.1315 These laboratory tests have been used to support clinical diagnosis, although these assays have proven to be unreliable due to the frequent false negatives.1315 The use of PCR assay may also aid in the diagnosis, using feces, blood, effusion, CSF, or tissue samples with inflammatory changes (omentum, lymph nodes, spleen). However, there are frequently inconsistent results for PCR assays performed on feces, blood effusion, CSF, or tissue samples from the same animal due to the dependence on the viral RNA load of each sample.15,16 Postmortem ancillary testing includes the use of immunohistochemistry and immunofluorescent antibodies on fixed and fresh samples, respectively.14 Even though direct immunofluorescent antibodies testing is positive in only 41% of infected fresh brain samples,11 it is still considered to be the fastest available postmortem diagnostic ancillary testing. A possible explanation for this high percentage of false-negative results is that the viral load on the CNS is low, compared with other tissues,14,17,18 and the viral distribution in the CNS differs depending on the predominant type of lesion, such as in periventricular encephalitis, rhombencephalitis, or diffuse leptomeningitis. Immunohistochemistry is a more reliable diagnostic tool with a reported sensitivity of 97% to 100% and specificity of up to 100%.19

References

  • 1.

    Townsend WM. Veterinary clinics small animal practice: canine and feline uveitis. Vet Clin Small Anim. 2008;38:323346.

  • 2.

    Colitz CMH. Feline uveitis: diagnosis and treatment. Clin Tech Small Anim Pract. 2005;20:117120.

  • 3.

    Andrew SE. Feline infectious peritonitis. Vet Clin North Am Small Anim Pract. 2000;30:9871000.

  • 4.

    Rohrbach BW, Legendre AM, Baldwin CA. Epidemiology of feline infectious peritonitis among cats examined at veterinary medical teaching hospitals. J Am Vet Med Assoc. 2001;218:11111115.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Hartmann K, Binder C, Hirschberger J, et al. Comparison of different tests to diagnose feline infectious peritonitis. J Vet Intern Med. 2003;17:781790.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Pesteanu-Somogyi LD, Radzai C, Pressler BM. Prevalence of feline infectious peritonitis in specific cat breeds. J Feline Med Surg. 2006;8:15.

  • 7.

    Worthing KA, Wigney DI, Dhand NK, et al. Risk factors for feline infectious peritonitis in Australia. J Feline Med Surg. 2012;14:405412.

  • 8.

    Foley JE, Poland A, Carlson J, Pedersen NC. Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus. J Am Vet Med Assoc. 1997;210:13131318.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Norris JM, Bosward KL, White JD, Baral RM, Catt MJ, Malik R. Clinicopathological findings associated with feline infectious peritonitis in Sydney, Australia: 42 cases (1990–2002). Aust Vet J. 2005;83:666673.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Grahn B, Peiffer G, Wilcock B. Histologic manifestations of disorders of the uvea. In: Grahn B, ed. Histologic Basis of Ocular Cisease. 1st ed. John Wiley & Sons, Inc; 2019:197253.

    • Search Google Scholar
    • Export Citation
  • 11.

    Rissi DR. A retrospective study of the neuropathology and diagnosis of naturally occurring feline infectious peritonitis. J Vet Diagn Invest. 2018;30(3):392399.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Addie D, Belák S, Boucraut-Baralon C, et al. Feline infectious peritonitis. ABCD guidelines on prevention and management. J Feline Med Surg. 2009;11:594604.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Boettcher IC, Matiasek K, Greene CE, Hartmann K, Fischer A. Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats. J Am Vet Med Assoc. 2007;230:199205.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Giori L, Giudice C, Grieco V, Paltrinieri S. Performances of different diagnostic tests for feline infectious peritonitis in challenging clinical cases. J Small Anim Pract. 2011;52:152157.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Kipar A, Meli ML. Feline infectious peritonitis: still an enigma? Vet Pathol. 2014;51:505526.

  • 16.

    Goodson T, Randell S, Moore L. Feline infectious peritonitis. Compend Contin Educ Vet. 2009;31:E18.

  • 17.

    Foley JE, Leutenegger C. A review of coronavirus infection in the central nervous system of cats and mice. J Vet Intern Med. 2001;15:438444.

  • 18.

    Foley JE, Rand C, Leutenegger C. Inflammation and changes in cytokine levels in neurological feline infectious peritonitis. J Feline Med Surg. 2003;5:313322.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Felten S, Hartmann K. Diagnosis of feline infectious peritonitis: a review of the current literature. Viruses. 2019;11(11):135.

Contributor Notes

Contributed equally to this work.

Corresponding author: Dr. Negrão Watanabe (tnegrao@ncsu.edu)