Wiener Tierärztliche Monatsschrift – Veterinary Medicine Austria 100 (2013) Aus der Tierärztlichen Klinik Birkenfeld1, Deutschland, und dem Labor Focus Veterinary Histopathology International2 , United Kingdom Cowpox virus infection in a cat in Southwest Germany a case presentation C. OUSCHAN1*, J. REST2 and S. PETERS1 received April 1, 2013 accepted May 28, 2013 Keywords: cowpox virus infection, cat, case report. Summary In Europe, the cowpox virus (CPXV) is one of the causes of skin diseases in domestic animals and humans with localized or disseminated appearance. Wood mice and particularly bank voles form the reservoir of the virus. Cats may be infected via contact with these rodents and are regarded as the main source of infection for humans. This case report describes a generalized CPXV skin infection in a cat with concurrent ulcerative stomatitis and a positive rapid test for feline leukaemia virus antigen. Histopathological examination of skin biopsies showed multifocal ulcerative to necrotizing dermatitis with typical epithelial eosinophilic intracytoplasmic inclusion bodies. Because of its zoonotic potential, cowpox virus infection should always be considered in the differential diagnosis of feline ulcerative dermatitis. Introduction According to genotypic data, cowpox virus (CPXV) is a composite of several (up to five) species that can infect various animals and humans (CARROLL et al., 2011). It belongs to the genus Orthopoxvirus, family Poxviridae. Wild rodents, especially bank voles (Myodes glareolus) and wood mice (Apodemus sylvaticus), seem to be the primary reservoir (CHANTREY et al., 1999; HAZEL et al., 2000). A study in the UK estimates that one in six wild mice hosts the virus (HAZEL et al., 2000). Cats are infected while hunting. Late summer and autumn are the main season for poxvirus infections in animals and humans, presumably due to the population peak of mice and voles at this time (KAYSSER et al., 2010). 326 Schlüsselwörter: Kuhpockeninfektion, Katze, Fallbericht. Zusammenfassung Kuhpockeninfektion bei einer Katze in Südwestdeutschland – eine Fallpräsentation Zusammenfassung Einer der Gründe für Hauterkrankungen bei Haustieren und Menschen, die sowohl lokalisiert wie disseminiert auftreten, ist das Kuhpockenvirus. Wald- und insbesondere Wühlmäuse sind für dieses Virus das Primärreservoir. Katzen können durch den Kontakt mit ihnen infiziert werden und stellen die wichtigste Quelle für die Infektion beim Menschen dar. Der vorliegende Bericht beschreibt einen Fall von generalisierten Hautveränderungen und Ulzerationen der Mundschleimhaut bei einer Hauskatze mit positivem Felinem Leukämievirus-Antigen. Die histopathologische Untersuchung der Veränderungen ergab eine multifokale, nekrotisierende Dermatitis mit für Poxvirusinfektionen typischen eosinophilen intrazyoplasmatischen Einschlusskörperchen. Aufgrund des zoonotischen Potenzials muss die Orthopoxvirus-Infektion in Fällen ulzerativer Dermatitiden bei Katzen differentialdiagnostisch besonders beachtet werden. Historically, cattle in contact with people were considered to be the species predominantly infected and thus the source for viral transmission to humans. Cowpox virus infections have a broad zoonotic potential (WOLFS et al., 2002; HERDER et al., 2011). Not only cattle but also pet rats (CAMPE et al., 2009; WOLFS et al., 2002), cats (THOMSETT et al., 1978; CHANTREY et al., 1999), dogs (VON BOMHARD et al., 2010) and humans (CZERNY et al., 1991; WOLFS et al., 2002; CAMPE et al., 2009; CARLETTI et al., 2009) may be affected. An infection in cats was first described by THOMSETT et al. (1978). Since then additional cases have been described in the UK (WEBSTER and JEFFERIES, 1984) and in other countries, including Germany (BALLAUF et al., 1989; MAHNEL, 1991; Wiener Tierärztliche Monatsschrift – Veterinary Medicine Austria 100 (2013) VON BOMHARD et al., 1992; KAYSSER et al., 2010; HERDER et al., 2011) and Austria (NOWOTNY et al., 1994). Recent studies describe cats as the primary source of human infection (CARLETTI et al., 2009); CPXV infection in dogs is very rare (VON BOMHARD et al., 2010). CPXV infection in cats usually leads only to cutaneous lesions. The disease is characterized by a primary solitary lesion occurring about six days post infection, followed by viraemia and widespread skin lesions approximately a week after the primary lesion. The lesions are usually not pruritic and the primary changes are mainly found on the anterior half of the body. According to the literature, males are more often affected, possibly because of their lifestyle. Secondary bacterial or fungal infections may worsen the skin lesions and cause progression (VON BOMHARD et al., 1992). With its zoonotic potential, cowpox virus infection should always be considered in the etiological differential in feline necrotizing dermatitis. Case Report The patient was ‘Mikesch’, a 10.5 year-old male castrated cat living mainly outdoors and vaccinated (Purevax® RCP, rabies). He received regular flea and tick prevention (Fipronil; Frontline® Spot On) and had been dewormed in late July 2011 (Milbemycin-Oxim, Praziquantel; Milbemax®). No other pets lived in the same household. History In October 2011, Mikesch disappeared for four days and returned with purulent crusts on the skin of one front paw. The first veterinarian consulted suspected a road traffic accident and started treatment with Meloxicam (Metacam®, 0.1 mg/kg SID s.c.), Marbofloxacin (Marbocyl®, 2 mg/kg SID p.o) and an Elizabethan neck collar. When the skin lesions worsened, Mikesch was given a cortisone depot injection (details not recorded). When the patient was presented at our referral clinic, the condition had deteriorated with spreading skin lesions affecting all four feet. By then, skin problems had been present for four weeks and the animal had not received any therapy for about a week. The owners had no skin lesions. On general clinical examination the cat was depressed, slightly pale and dehydrated. A complete dermatological examination was performed. Both front paws presented swollen, ulcerative lesions of 0.5 to 1.5 cm in diameter that bled on pressure. The nose showed an alopecic crusty spot of about 0.5 cm in diameter. Multiple smaller lesions were distributed over the body. Cytological examination of impression smears showed intracellular coccal bacteria, degenerated neutrophils and some acantholytic epithelial cells. Fig. 1: Alopecic crusty spot, about 0.5 cm in diameter, on the nose of a cat with cowpox infection With the exception of a slightly elevated level of creatinine, haematological and biochemical examinations showed no abnormalities. The creatinine level was within the reference range on subsequent testing. The rapid screening test for feline leukaemia virus (FeLV) antigen was positive, while the rapid screening test for feline immunodeficiency virus (FIV) antibodies was negative (SNAP Combo plus®). The ANA (anti-nuclear antibody) test was negative. Protein electrophoresis showed an elevated alphaglobulin, consistent with an acute inflammatory disease. The owners were informed about the risk of anaesthesia due to the FeLV status. The cat was anaesthetized with butorphanol (Dolorex®) as premedication and propofol (Propofol®) for maintenance. Seven skin biopsies were taken to distinguish the potential clinical diagnoses (bacterial and fungal Fig. 2: Cat with cowpox infection showing multiple lesions all over the body, especially on the paws 327 Wiener Tierärztliche Monatsschrift – Veterinary Medicine Austria 100 (2013) infections, eosinophilic granuloma, virus infection, autoimmune disease and neoplasia; MILLER et al., 2013). The biopsies were sent to Focus Veterinary Histopathology International (Great Britain). Histopathology The thick crust was colonized by bacteria but did not contain any acantholytic cells. The epidermis had sharply demarcated necroses and ulcerations. Intracytoplasmic angular accumulations of eosinophilic material varying in size from 7-14 μm were present focally in surviving surface and follicular epithelium. The dermis had a perifollicular infiltrate including macrophages, neutrophils and lymphocytes with necrosis of hair follicles. No mites, yeasts or fungi were seen. The morphological diagnosis was deep necrotizing folliculitis and dermatitis. The eosinophilic accumulations in the epithelium were consistent with viral inclusion bodies indicating an orthopox infection (cowpox or catpox). The finding of characteristic inclusion bodies with compatible histopathology is an accepted method for confirming the diagnosis of pox infection (GROSS et al., 2005). No further examination (PCR) was undertaken because of characteristic finding of inclusion bodies. The finding of characteristic inclusion bodies with compatible histopathology is an accepted method for confirming the diagnosis of pox infection (GROSS et al., 2005). Therapy There is no specific therapy for poxvirus infection. Broad-spectrum antibiotics to prevent secondary bacterial infections are recommended, while glucocorticoids are contraindicated (MILLER et al., 2013). In this case the cat was given amoxicillin-clavulanic acid 25 mg/kg BID (Amoxclav Hexal Injektionslösung 500/100 mg) and enrofloxacin (Baytril®, 5 mg/kg p.o. SID). He was also given analgesics: buprenorphine (Temgesic®, 0.1 mg/kg TID) and meloxicam (Metacam®; 0.1 mg/kg s.c. SID). The crusty lesions were carefully bathed with chlorhexidine (4%) in a diluted solution (1:6). Precautions were taken against transmission to humans. The skin lesions improved during treatment. The feet became less swollen and the inflammation reduced. The general demeanour of the cat improved, but after a week, the cat again became lethargic, refused to eat and clinical examination showed new skin lesions and ulceration and inflammation of the oral cavity. With progression of clinical disease and poor prognosis, the cat was euthanized. The owners refused further pathological examination. Sources of Supply Purevax® RCP, Tollwut, Merial, Germany; Fipronil (Frontline® Spot On, Merial, Germany); Milbemycin-Oxim und Praziquantel (Milbemax®, Novartis, Germany); Meloxicam (Metacam®, Böhringer Ingelheim-Vetmedica GmbH, Ingelheim, Germany); Marbofloxacin (Marbocyl®, Vetoquinol GmbH, Germany); butorphanol 328 Fig. 3: Histopathology of a skin biopsy of a cat with cowpox infection: The epidermis is poorly stained because there is significant necrosis. Central nuclei show karryorhexis. Red intracytoplasmic pox inclusion bodies can be seen in the cytoplasm of residual epithelial cells (arrows) (arrows; H&E, x400). (Dolorex®, Intervet, Germany); propofol (Propofol®, Norbrook Laboratories Ldt, UK; Alfavet Tierarzneimittel GmbH, Neumünster, Germany); amoxicillin clavulanicacid (Amoxclav Hexal Injektionslösung 500/100 mg, Hexal AG, Germany); enrofloxacin (Baytril®, Bayer, Germany); buprenorphine (Temgesic®, Bayer Vital, Kiel), Deutschland; rapid screening test for Feline Immunodeficiency Virus (SNAP Combo plus®, Idexx laboratories, IDEXX Europe B.V.; P.O. Box 1334; NL-2130; EK Hoofddorp). Discussion The present case describes a generalized cowpox virus infection in a cat, which was diagnosed in autumn. Most feline CPXV infections occur in late summer to autumn, when rodent reproduction usually peaks. An extremely mild winter in 2007 caused an increased population of voles and the highest number of CPXV infections in cats in Germany in late summer 2008 (KAYSSER et al., 2010). The disease is a zoonosis and infected cats represent a potentially serious threat to their owners (LUBACH, 1992). The infection is transmitted by close contact with infected animals. CPXV has been shown to have been transmitted from pet rats to humans (BECKER et al., 2009; CAMPE et al., 2009) and from cats to humans (MAHNEL, 1991; VON BOMHARD et al., 1992). As vaccinia virus vaccination was discontinued in the 1980s, cowpox virus infections are steadily increasing in Europe (BLACKFORD et al., 1993; HERDER et al., 2011). The disease is usually mild in humans but children and immune-suppressed people are severely compromised. In the present case, the owners were an elderly couple with close contact with their cat. Neither of them developed any clinical signs of poxvirus infection, possibly because of immune protection from their vaccinia vaccination. Wiener Tierärztliche Monatsschrift – Veterinary Medicine Austria The prognosis for cowpox is generally good. Secondary bacterial or fungal infections may worsen the skin lesions and cause their progression. Approximately 20% of infected cats develop oral vesiculation or ulceration (MILLER et al., 2013). The cat in this case also developed ulcerative glossitis, due to the CPXV or to another infection. Generalized CPXV infections are usually associated with underlying immunosuppressive conditions, such as infection with FeLV, parvovirus (SCHAUDIEN et al., 2007) or FIV. Therapy with corticosteroids is therefore generally contraindicated. As shown in the present case, concurrent FeLV infection and corticosteroid therapy may lead to a severe generalized systemic infection. There is only one reported case of recovery from pneumonia in which both poxvirus and feline herpes virus were found (JOHNSON et al., 2009). Fatal necrotizing pox viral 100 (2013) pneumonia without skin lesions was recorded in 2007 (SCHÖNIGER et al., 2007). The infection may be misdiagnosed. Lesions induced by poxvirus bear a macroscopic resemblance to herpes virus 1-associated facial and nasal dermatitis and stomatitis (HARGIS and GINN, 1999) but are histologically distinct. Other clinical differential diagnoses are eosinophilic granuloma, pyoderma, other viral infections, autoimmune diseases such as pemphigus foliaceus or neoplasia, all of which can be distinguished by histopathology. Diagnosis of CPXV infection is based on clinical appearance and histopathology – typical inclusion bodies in epithelial cells indicate the diagnosis – or PCR of skin lesions. As such infections are becoming more frequent, we hope this case report will raise public awareness and reduce the individual risk of human infection. References BALLAUF, B., LINCKH, S., LECHNER, J. (1989): Pockeninfektion bei einer Katze. Tierärztl Prax 17, 408–411. BECKER, C., KURTH, A., HESSLER, F., KRAMP, H., GOKEL, M., HOFFMANN, R., KUCZKA, A., NITSCHE, A. (2009): Kuhpocken bei Haltern von Farbratten. 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