Scientific Papers

Virulent systemic feline calicivirus infection: a case report and first description in Ireland | Irish Veterinary Journal

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Feline calicivirus (FCV) is a small, single-stranded RNA virus belonging to the Caliciviridae family [1]. Feline calicivirus is widespread in the general cat population, with prevalence ranging from 2.5% in households with less than 4 cats, up to 90% in high-density cat colonies [2]. This high prevalence is explained by the ability of feline calicivirus to persist asymptomatically in the retropharyngeal area of some cats [2, 3]. Feline calicivirus has been shown to be able to evade the host’s immune response through different mechanisms in healthy carrier cats [4], allowing them to become lifelong shedders [5]. Cats are infected through the nasal, oral or conjunctival routes [4]. The infection can be direct, from cat to cat, or indirect via fomites and possibly aerosols [6].

The classic form of the disease is usually characterized by acute, self-limiting upper respiratory tract signs, and less commonly a lameness syndrome or severe pneumonia [4, 5, 7]. Feline calicivirus has also been associated with chronic gingivostomatitis [8].

Due to the viral characteristics (lack of proof-reading and low fidelity), the virus has an important genetic plasticity, which allows it to mutate quickly [7]. The high prevalence combined with the ubiquitous distribution of the virus in the feline population, further increases the likelihood of recombination events and mutations [4]. Thus, there is a high potential for emergence of strains with increased pathogenicity and systemic tropism [9]. Different mutated strains have already been isolated and reported [10, 11].

In the past 25 years, a virulent systemic form of feline calicivirus has been reported in the United States, continental Europe, the United Kingdom, and Australia: virulent systemic feline calicivirus (VS-FCV) [12,13,14,15,16,17,18,19]. It is known to affect cats that have been appropriately vaccinated against feline calicivirus infection [7]. These highly-contagious strains resulting in devastating nosocomial infections have been reported with one single cat suspected of having infected nine other cats in one study [18], as well as outbreaks affecting up to 54 cats [14].

Feline calicivirus binds to a receptor that is located at the tight junctions of endothelial and epithelial cells [7]. This receptor regulates the integrity and permeability of the cell layers [7]. Their disruption leads to oral ulceration in the classic form, and cutaneous ulceration in the virulent systemic form. Vasculitis also plays a role in the pathogenesis of the latter form, and notably participates in the development of cutaneous lesions, oedema, and additional systemic consequences [20]. Although the exact pathogenesis of VS-FCV infection remains poorly understood, it likely involves different cell tropism allowing involvement of visceral organs and systemic involvement and more rapid growth compared to less virulent strains [1, 7, 21]. The vascular damage identified on histopathology are likely immune-mediated and potentially involving local cytokine modulation [21].

The mortality rate for VS-FCV ranges from 22 to 86% depending on the outbreak [19]. Survivors have complete resolution of clinical signs, usually within 7–10 days [12, 16], although duration of clinical signs for up to 40 days have been reported [13, 19].

Whilst highly contagious, basic environmental management (disinfection with sodium hypochlorite, potassium peroxymonodysulfate, chlorine dioxide and commercial products approved for calicivirus inactivation) and isolation measures are effective in preventing spread to other cats [22, 23].

Infection with VS-FCV has not yet been reported in Ireland. However, calicivirus is prevalent in the feline population on the island of Ireland [24]. High-density shelters are present in the country, providing a possible reservoir for emerging mutated calicivirus strains with potential for virulent systemic calicivirus emergence.

This case report provides information on the first endemic case of non-epizootic VS-FCV infection in a cat from Ireland.

Case presentation

An 11-month-old male neutered domestic shorthair cat was presented with a 10-day history of lethargy, decreased appetite, pyrexia and progressively worsening pitting oedema affecting all four limbs.

The cat was indoor-outdoor, and up-to-date regarding routine vaccination and parasite treatment. It had never travelled outside Ireland. A few days prior to the onset of the clinical signs, a 3-month-old kitten had been adopted from a shelter. The kitten was reported to be free of clinical signs.

The first documented clinical sign in the cat was self-limiting non-weight-bearing lameness of the left pelvic limb. Investigations performed by the referring veterinarian identified mild leukocytosis (18.67 (reference interval 6–18) × 109/L) with neutrophilia (16.8 (reference interval 2.5–12.5) × 109/L) and moderate-to-marked thrombocytopenia (57 (reference interval 180–550) × 109/L) likely related to platelet clumping (adequate platelets on blood smear examination). Enzyme-linked immunosorbent assay (ELISA) for feline immunodeficiency virus (FIV) antibody and feline leukaemia virus (FeLV) antigen were negative. Treatment with cefovecin and non-steroidal anti-inflammatory drugs (NSAID) resulted in a mild transient improvement of the clinical signs. However, there was progressive pitting oedema affecting all four limbs and persistent pyrexia, prompting referral.

Upon referral, physical examination identified increased rectal temperature (40.2 °C). There was severe pitting oedema in all four limbs, with an exudative and ulcerative cutaneous lesion (2 cm diameter) on the cranio-distal aspect of the left pelvic limb (Fig. 1). Buccal examination identified 3 superficial erosions on the dorsal aspect of the tongue (Fig. 2).

Fig. 1
figure 1

Photograph of the swelling of both thoracic limbs on presentation (A), cutaneous ulceration the tibial cranial area of the left pelvic limb (B) and exudative lesion after clipping of the right pelvic limb (C)

Fig. 2
figure 2

Photograph of the lingual erosions and ulcerations on presentation

The problem list included non-antimicrobial responsive progressively worsening diffuse pitting edema in all-four limbs with cutaneous ulcerations, lingual ulcers and moderate-to-marked pyrexia.

The main differential diagnoses for pyrexia, considering the age and the history, included infectious or inflammatory causes, and less likely neoplasia. The ulcerative lesions in the tongue could be caused by infectious conditions including calicivirus and herpesvirus infections. Mechanical or toxic causes (e.g., foreign body, uraemia, caustic agent) were considered less likely given the subacute worsening clinical progression, the presence of systemic signs and the prior laboratory results. Inflammatory and neoplastic conditions were considered less likely but not ruled out.

The oedema in all-four limbs could have been caused by increased vascular permeability, increased hydrostatic pressure (e.g., right-sided congestive heart failure, venous thromboembolism), decreased oncotic pressure (e.g., hypoalbuminaemia), or diffuse lymphatic disorders (e.g., lymphangitis, lymphoedema). Given the presence of cutaneous and lingual ulcerations, increased vascular permeability related to diffuse vasculopathy was suspected. Differentials included primary inflammatory vasculitis or secondary vasculitis (infectious with bacterial sepsis, mycobacteria, virulent systemic calicivirus, drug-induced, insect bite-induced).

The cat was hospitalized in the isolation unit with barrier nursing and adequate disinfection given the potential risk of virulent systemic calicivirus or mycobacterial infection. Management included intravenous fluid therapy and analgesia (buprenorphine, 15 ug/kg four times daily) which was facilitated by the placement of a venous central line. Peripheral venous access was not possible given the marked oedema affecting all limbs.

Follow-up haematology identified persistent leukocytosis (29.37 reference interval 6–18) × 109/L) with neutrophilia (27.75 (reference interval 2.5–12.5) × 109/L) and mild lymphopenia (0.92 (reference interval 1.5–7) × 109/L) consistent with non-specific inflammation, infection or a stress leukogram. Biochemistry was largely unremarkable. Thoracic radiographs and abdominal ultrasound were performed to investigate for an underlying trigger or an infectious focus. These examinations were unremarkable. As an infectious aetiology was suspected, multimodal testing was performed. Blood cultures were negative. Culture of the exudative cutaneous lesion on the pelvic limb was negative. A skin biopsy was performed on the right lateral antebrachium. The area sampled was oedematous but unfortunately did not include any ulcerative lesion. Histopathological examination identified oedema without other pathological changes. Culture of the skin biopsy identified a light growth of Enterococcus faecalis susceptible to marbofloxacin. Secondary bacterial infection could not be ruled out. Ziehl–Neelsen staining of the biopsy was negative, providing no support for mycobacterial infection. Polymerase chain reaction (PCR) performed on oropharyngeal sampling was negative for herpesvirus and reverse-transcriptase (RT) PCR was positive for calicivirus (Idexx ®Laboratories UK). Blood RT-PCR was positive for calicivirus (Scanelis ®Laboratories France).

Based on these results, a presumptive diagnosis of VS-FCV infection was made. However, given the persistent pyrexia, the necrotic appearance of the ulcerative lesions and the positive bacterial culture of the skin biopsy that had initially raised concerns of secondary bacterial infection, intravenous antimicrobial therapy (marbofloxacin, 2 mg/kg) was continued. Given the persistent pyrexia despite treatment with NSAID, intravenous corticosteroid therapy at an anti-inflammatory dose (dexamethasone, 0.1 mg/kg) was initiated after allowing a three-day wash-out period. The clinical signs progressively improved over six days and spontaneous appetite returned. Given the concern for the highly contagious nature of the virus for other cats in the hospital and in face of the progressive clinical improvement, the cat was discharged with oral corticosteroid (prednisolone, 0.5 mg/kg once daily) and antimicrobial therapy (marbofloxacin 2 mg/kg once daily). Daily follow-up over the phone were performed. The owners provided pictures to monitor the satisfactory progression of the cutaneous lesions (Fig. 3).

Fig. 3
figure 3

Progression of the cutaneous ulceration on presentation (A), on discharge after 6 days (B), and at home after one week (C)

One month after discharge, the cat was reassessed. There was a complete resolution of all clinical signs (Fig. 4). Repeat blood RT-PCR was negative. Blood RT-PCR was also performed on the adopted kitten and was negative.

Fig. 4
figure 4

Complete resolution of the cutaneous signs 2 months after presentation (B) compared to immediately after discharge (A)

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