History
Three approximately 4-week-old eastern gray squirrel siblings (Sciurus carolinensis) believed to be orphaned were brought to the University of Illinois Wildlife Medical Clinic.
Clinical and Gross Findings
At the initial evaluation, physical examination revealed that one of the squirrels had firm, raised, hairless, hyperemic nodules (approx 0.2 to 0.5 cm in diameter) on the right forelimb and near the tail base. Out of concern that the nodules were caused by an infection and were potentially painful, this squirrel (a female) was treated orally with meloxicam and amoxicillin trihydrate potentiated with potassium clavulanate. While hospitalized, the littermates were kept together in an incubator and provided supplemental feedings by bottle every 3 hours. Five days after initial evaluation, the affected squirrel was found deceased; necropsy was not performed. Prior to death, the squirrel developed no additional clinical signs besides developing additional skin nodules on the dorsum and ventrum. At this time, the remaining 2 squirrels were noted to have skin nodules as well as plaques, which had not been detected in their littermate. The squirrels progressively became lethargic and anorexic. These animals also received meloxicam and amoxicillin trihydrate potentiated with potassium clavulanate orally. Because of severe deterioration in its condition, 1 squirrel (a male) was euthanized 20 days after admission; to perform euthanasia, the squirrel was administered isoflurane via face mask until a deep level of anesthesia was achieved (no response to noxious stimuli) followed by intracardiac injection of pentobarbital solution. The squirrel was submitted for necropsy. At 28 days after admission, the third squirrel (a female) was similarly euthanized because of its poor prognosis and submitted for necropsy.
At necropsy, both squirrels were in fair to poor body condition with minimal to absent subcutaneous and visceral adipose tissue stores. The skin overlying the dorsal aspect of the head of the male squirrel was focally alopecic (affected area, 2 × 1 cm). Additionally, the skin overlying the dorsum had a 1-cm, circular, crusted, white to tan plaque. The ventral aspect of the right lung lobes contained multiple, pinpoint, white to gray, sharply demarcated soft nodules. Extending from the capsular surface to the corticomedullary junction of the cranial pole of the left kidney were two 2-mm, circular, white to tan soft nodules.
Multifocally, the skin overlying the dorsum, ventrum, inguinal regions, and right hind limb of the female squirrel contained multiple 0.1- to 1.5-cm-diameter, multifocally raised (0.2-cm), crusted, red to tan, alopecic plaques and nodules (Figure 1). The pinna on the left ear was diffusely thickened (0.2 cm), alopecic, and mottled red to tan. The lower left eyelid was focally thickened (0.1 cm) and alopecic.
Photographs of the inguinal region (A) and dorsum (B) of an approximately 4-week-old female eastern gray squirrel. In panel A, notice the raised nodular masses present on the left flank and right inguinal region, which developed subsequent to similar signs being noted in a littermate. In panel B, notice the nodular, scabbed mass over the epaxial muscles.
Citation: Journal of the American Veterinary Medical Association 245, 4; 10.2460/javma.245.4.389
Photographs of the inguinal region (A) and dorsum (B) of an approximately 4-week-old female eastern gray squirrel. In panel A, notice the raised nodular masses present on the left flank and right inguinal region, which developed subsequent to similar signs being noted in a littermate. In panel B, notice the nodular, scabbed mass over the epaxial muscles.
Citation: Journal of the American Veterinary Medical Association 245, 4; 10.2460/javma.245.4.389
Photographs of the inguinal region (A) and dorsum (B) of an approximately 4-week-old female eastern gray squirrel. In panel A, notice the raised nodular masses present on the left flank and right inguinal region, which developed subsequent to similar signs being noted in a littermate. In panel B, notice the nodular, scabbed mass over the epaxial muscles.
Citation: Journal of the American Veterinary Medical Association 245, 4; 10.2460/javma.245.4.389
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic Findings
Multiple tissues, including skin, spleen, kidneys, heart, liver, intestines, and lungs, from both squirrels were submitted for histologic examination. The skin lesions of both squirrels were characterized by moderate to marked epidermal hyperplasia with ballooning degeneration, small to moderate numbers of intraepidermal neutrophils, a few intracorneal pustules, and many circular (5- to 10-m-diameter), intraepithelial eosinophilic intracytoplasmic inclusion bodies (Figure 2). In these regions, the dermis was mildly to markedly expanded by streams of atypical spindle-shaped mesenchymal cells containing oval to elongate nuclei and many circular (5- to 10-μm-diameter), eosinophilic, intracytoplasmic inclusion bodies. Intervening dermal mesenchymal cells were small numbers of viable and necrotic neutrophils, fewer lymphocytes, and plasma cells. The renal interstitium of both squirrels was multifocally mildly expanded by small numbers of similar atypical mesenchymal cells with rare eosinophilic intracytoplasmic inclusion bodies as for the dermis (Figure 3). The jejunal lamina propria and submucosa as well as the pulmonary perivascular and alveolar interstitium of the male squirrel was multifocally, mildly expanded by small numbers of similar atypical mesenchymal cells with few eosinophilic intracytoplasmic inclusion bodies as for the dermis. Affected alveolar septae were multifocally lined by cuboidal pneumocytes (type II pneumocyte hyperplasia) and contained many intraepithelial, circular (5- to 10-μm diameter), eosinophilic intracytoplasmic inclusion bodies. Throughout the lungs, many alveolar spaces and few terminal bronchioles contained moderate amounts of edema and many foamy macrophages. No major lesions were observed in any other organs.
Photomicrographs of a section of haired skin from a male littermate of the squirrel in Figure 1. In the main low-magnification image, there is marked dermal expansion by atypical mesenchymal cells and epidermal hyperplasia with ballooning degeneration and hyperkeratosis. H&E stain; bar = 200 μm. Inset—Multiple epidermal epithelial cells and atypical dermal mesenchymal cells contain 5- to 10-μm-diameter eosinophilic intracytoplasmic inclusion bodies (arrows). H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 245, 4; 10.2460/javma.245.4.389
Photomicrographs of a section of haired skin from a male littermate of the squirrel in Figure 1. In the main low-magnification image, there is marked dermal expansion by atypical mesenchymal cells and epidermal hyperplasia with ballooning degeneration and hyperkeratosis. H&E stain; bar = 200 μm. Inset—Multiple epidermal epithelial cells and atypical dermal mesenchymal cells contain 5- to 10-μm-diameter eosinophilic intracytoplasmic inclusion bodies (arrows). H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 245, 4; 10.2460/javma.245.4.389
Photomicrographs of a section of haired skin from a male littermate of the squirrel in Figure 1. In the main low-magnification image, there is marked dermal expansion by atypical mesenchymal cells and epidermal hyperplasia with ballooning degeneration and hyperkeratosis. H&E stain; bar = 200 μm. Inset—Multiple epidermal epithelial cells and atypical dermal mesenchymal cells contain 5- to 10-μm-diameter eosinophilic intracytoplasmic inclusion bodies (arrows). H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 245, 4; 10.2460/javma.245.4.389
Photomicrograph of a section of kidney tissue from the male squirrel in Figure 2. The renal interstitium is expanded by atypical mesenchymal cells containing eosinophilic intracytoplasmic inclusion bodies (arrows). H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 245, 4; 10.2460/javma.245.4.389
Photomicrograph of a section of kidney tissue from the male squirrel in Figure 2. The renal interstitium is expanded by atypical mesenchymal cells containing eosinophilic intracytoplasmic inclusion bodies (arrows). H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 245, 4; 10.2460/javma.245.4.389
Photomicrograph of a section of kidney tissue from the male squirrel in Figure 2. The renal interstitium is expanded by atypical mesenchymal cells containing eosinophilic intracytoplasmic inclusion bodies (arrows). H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 245, 4; 10.2460/javma.245.4.389
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: moderate to severe, multifocal, proliferative dermatitis with atypical dermal mesenchymal cell hyperplasia, epithelial, and mesenchymal cell intracytoplasmic eosinophilic inclusion bodies; mild, multifocal, suppurative dermatitis (male and female squirrels); multifocal interstitial atypical mesenchymal cell hyperplasia with intracytoplasmic eosinophilic inclusion bodies in the kidney tissue (male and female squirrels); multifocal interstitial atypical mesenchymal cell hyperplasia with intracytoplasmic eosinophilic inclusion bodies in the jejunum (male squirrel); multifocal interstitial atypical mesenchymal cell hyperplasia and type II pneumocyte hyperplasia with epithelial and mesenchymal cell intracytoplasmic eosinophilic inclusion bodies in the lung tissue; and moderate, multifocal, subacute, pulmonary edema (male squirrel).
Case summary: cutaneous and disseminated infection with squirrel fibroma virus (SFV) in 4-week-old eastern gray squirrel littermates.
Comments
The gross and histopathologic lesions of the squirrels of the present report represented typical findings of cutaneous and disseminated infection with SFV. This viral disease is known to affect eastern gray squirrels, western gray squirrels (Sciurus griseus), and American red squirrels (Tamiascurius hudsonicus); presumptive infection has been reported for a fox squirrel (Sciurus niger).1–5 In an experimental setting,6 this virus also induces disease in domestic rabbits (Oryctolagus sp) and woodchucks (Marmoto monax). The etiologic agent is a poxvirus in the Leporipoxivirus clade of the subfamily Chordopoxvirinae.7 Given the similarity of gross and histopathologic lesions, immunologic cross-reaction, and virus ultrastructure, researchers consider SFV to be closely related to the rabbit fibroma virus (Shope fibroma virus).8 Squirrel fibroma virus–associated disease develops sporadically, although an epizootic among gray squirrels was reported in Florida in 2002.9
Squirrel fibromatosis develops most commonly in a cutaneous form but may develop as a fatal disseminated form with visceral nodules.10,11 The exact vectors of the virus are unknown; however, transmission through bites of arthropods such as the squirrel flea (Orchopeus howardi) has been proposed. Additionally, mosquitoes (Aedes aegypti and Anopheles quadrimaculatus) have been shown experimentally to transmit the disease.6 The presence of multiple cutaneous nodules may be a result of multiple exposures to insect vectors or disseminated viral disease. A previous investigation12 linked the pulmonary form (as developed in the male squirrel of the present report) to intratracheal inoculation, although viremia is also a possible source. The presence of nodules in other visceral organs (eg, kidneys) is considered secondary to viremia.4 The incubation period is thought to be 10 days, with viremia and resultant metastasis of cutaneous nodules occurring 2 to 3 weeks later.6 Given this timeline, it is thought that the squirrels of this report were inoculated by arthropod vectors prior to hospital admission, and they developed viremia while in the hospital.
A nodular skin disease with similar gross lesions is bot fly larva (Cuterebra spp) infestation. Infestation by larvae of bot flies, which are pervasive all over the eastern United States, should be considered as a differential etiologic diagnosis for nodular skin lesions in squirrels. The nodules, also called warbles, commonly affect the flank and shoulder regions and are typically larger than nodules caused by SFV.13 Moreover, warbles each contain an opening through which the larva can breathe and often seep a serosanguineous discharge. After the larva emerges from the warble, the nodule regresses within 10 days.14
Squirrel poxvirus (SPV) is another viral cause of nodular skin lesions in squirrels and accounts for the serious decrease in the number of European red squirrels (Sciurus vulgaris) of the United Kingdom.15,16 Although previously thought to be a Parapoxvirus, recent molecular characterization suggests that SPV has its own clade in the Chordopoxvirinae subfamily.17 There is no published report of SPV detection in North America, to our knowledge. However, serum anti–SPV antibodies have been identified in American red squirrels from Dane County, Wis.17 Squirrel poxvirus– associated lesions are severe, ulcerative, and hemorrhagic. In contrast, SFV infection results in formation of distinct individual to multiple cutaneous and visceral nodules.4,5
Antemortem diagnosis of squirrel fibromatosis is typically based on gross lesions, although atypical mesenchymal cell hyperplasia, eosinophilic intracytoplasmic inclusion bodies, and other histopathologic lesions such as those observed in the 2 squirrels of this report strengthen clinical suspicion of this disease. Antemortem or postmortem definitive diagnosis can be obtained through PCR assay or electron microscopy of a skin biopsy specimen.1 However, in wildlife rehabilitation settings, these diagnostic testing procedures are rarely used because of financial constraints.
Similar to rabbit fibromatosis, squirrel fibromatosis usually regresses suddenly.18 It has been suggested that the immunologic incompetence of juvenile squirrels results in a higher frequency of disseminated viral disease and associated higher mortality rate.3,4 In a wildlife rehabilitation setting, supportive treatment may enhance likelihood of survival of a mildly or moderately affected squirrel to discharge from the hospital; if rehabilitators pursue treatment, affected animals should be kept isolated from conspecifics and control measures should be implemented against potential arthropod vectors. Given the grave prognosis, severely affected squirrels, including those with the disseminated form of the disease, should be euthanized.
References
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