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Godfrey 25/3/04 13:07 Page 202

Unusual presentations of
cowpox infection in cats
Cowpox virus infections are reported typically to cause focal (Bennett and others 1999). Pneumonia is
a severe complication which is occasion-
ulcerated, crusted skin lesions, sometimes with mild systemic
ally associated with cowpox infection but
illness and concurrent oral lesions. Severe systemic illness usually there are only two detailed case reports
documenting this in cats (Hinrichs and
only occurs in young or immunosuppressed individuals. This report
others 1999, Hübner 2002). To date, cases
describes four cases of cowpox infection in cats which illustrate with signs confined to oral lesions have not
been reported. Likewise, cases that have
variations to the usual presentation of the virus. The poxvirus
exhibited large areas of skin necrosis,
infections were confirmed histopathologically, serologically and by intractable oedema or loss of digits are
not recorded in the existing veterinary
PCR analysis.
literature.

D. R. GODFREY, C. J. BLUNDELL, INTRODUCTION CASE HISTORIES


S. ESSBAUER*, M. PFEFFER*,
D. H. SHEARER†, J. R. REST‡ Cowpox virus is an Orthopoxvirus found Case 1
ft AND J. F. M. BAKER†
only in Western Europe and Asia. The dis- A four-year-old, neutered male, domestic
Journal of Small Animal Practice (2004)
ease it causes in cats has been called ‘feline shorthair cat presented with an acute-
45, 202–205 cowpox’ and ‘catpox’. Wild rodents seem onset, non-pruritic dermatosis in August
e to be a reservoir for cowpox virus (Maren- 1999. The animal was a rodent hunter and
o nikova and others 1978, Kaplan and oth- showed no evidence of systemic disease.
ers 1980, Bennett and others 1999, There was no history of previous der-
Chantrey and others 1999, Hazel and oth- matoses and no evidence of contagion to
ers 2000, Wolfs and others 2002). Cases in humans or in-contact pets. The skin
domestic cats are typically seen in the lesions were confined to the lips and were
e autumn, and are associated with the peak bilateral and roughly symmetrical. They
population of the rodent hosts (Chantrey consisted of ulceration with small areas of
and others 1999, Pfeffer and others 2002). dark brown crust (Fig 1). Under general
Human infections in Great Britain are anaesthesia, three ulcers (<5 mm diameter)
Nine Lives Veterinary Practice for Cats, reported to be in single figures per year and were found on the caudal tongue and soft
2068 Stratford Road, Hockley Heath, West
Midlands B94 6NT
are often associated with disease in pet palate. There was moderate bilateral
*World Health Organization Centre for Collection
cats (Baxby and others 1994, Baxby and enlargement of the submandibular lymph
and Evaluation of Data on Comparative Virology, Bennett 1997). nodes. No other lesions were found on
Consulting Laboratory for Poxviruses, In cats, the typical initial skin lesion is thorough examination.
Institute of Medical Microbiology, Infectious
and Epidemic Diseases, Veterinärstrasse 13, an ulcerated nodule with crust, usually Punch biopsies were taken from the
D-80539 Munich, Germany on the head or forelimbs. This is the site lip lesions. Histopathology of the muco-
†Finn Pathologists, Weybread, Diss, where the cat will have had direct contact cutaneous junction showed hydropic de-
Norfolk IP21 5TT with the rodent and local virus replication generation of keratinocytes; eosinophilic,
‡24 Lower End, Swaffham Prior, has occurred. After one or two weeks, sec- intracytoplasmic inclusion bodies; and
Cambridge CB5 0HT
ondary skin lesions appear. They start as deep dermatitis with perifolliculitis, folli-
C. J. Blundell’s present address is The
Oxfordshire Cat Clinic, Larkmead Veterinary macules or small erythematous nodules culitis and furunculosis (Fig 2). This was
Group, Cholsey, Oxfordshire OX14 9PA that often ulcerate, scab and later heal, considered consistent with cowpox infec-
M. Pfeffer’s present address is Institute producing scarring (Bennett and others tion. Embedded tissue was deparaffinised
of Microbiology, German Armed Forces,
Neuherbergstrasse 11, D-80937 Munich,
1999). Concurrent oral lesions have been with xylene (Merck), rehydrated and
Germany reported to occur in about 20 per cent of washed in phosphate-buffered saline.
D. H. Shearer’s present address is Vetcutis, feline cases (Bennett and others 1990). DNA was extracted using the QIA Mini
Holly House, Pulham St Mary, Diss, Norfolk The appearance of systemic signs is Kit (Qiagen; Hilden). A PCR with primers
IP21 4QQ
unusual, other than mild pyrexia, depres- targeting the Orthopoxvirus gene of the 14
J. F. M. Baker’s present address is Patolovet-
Patologia Veterinaria Unipessoal, Lda. Av. Duarte sion and occasionally diarrhoea, which kDa protein (A27L) was performed, as
Pacheco, 232. 8135-104 Almancil, Portugal are associated with transient viraemia described by Essbauer and others (2002).

202 JOURNAL OF SMALL ANIMAL PRACTICE • VOL 45 • APRIL 2004


Godfrey 25/3/04 13:07 Page 203

FIG 2. Diagnostic eosinophilic intracytoplasmic inclusion bodies in the


keratinocytes of the epithelium in case 1. Haematoxylin and eosin. 250

FIG 1. Gross appearance of the skin lesions on presentation of case 1.


The lesions were bilateral

DNA of vaccinia virus strain Munich 1 paw and over the triceps muscle. There
was used as a positive control. The finding was an area of necrotic skin (2 cm diame-
of 280 bp-sized DNA fragments (Fig 3) ter) on the dorsal aspect of the paw,
was a positive result. A second PCR, spe- extending distally on to the proximal por-
cific for the gene encoding the acidophilic tion of the dorsal aspect of digits II to IV.
inclusion protein A-type inclusion body There was widespread erythema. A few
(ATI), as described by Meyer and others macules, nodules and crusted nodular
(1994), was performed. This was also pos- lesions were seen scattered on the lateral
itive (data not shown). aspect of the upper leg, the left flank and
Treatment with 5 mg/kg clindamycin the head. The rectal temperature was con-
(Antirobe; Pharmacia & Upjohn) was sidered to be slightly high (39·5°C).
given orally, twice a day, for 10 days. The A wedge biopsy was taken from the
cat completely recovered in less than three lower leg. Histopathology showed spon-
weeks and no lesions reappeared in the giosis, necrosis and ulceration of the
subsequent two years. epidermis, with intracytoplasmic eosino-
philic inclusion bodies of varying size in
Case 2 the surviving epithelium. The dermis and
A four-year-old, rodent-hunting, neutered subcutis had dense inflammatory infil-
female, domestic shorthair cat presented in trates of mononuclear cells and neu-
May 2000 with left foreleg lameness of one trophils with necrosis. A piece of crust
day’s duration. The leg was moder- taken from the foreleg was positive for
ately swollen from the paw to the elbow. poxvirus by isolation in feline kidney
There was a 1 cm erosion on the landing cells and vero cells. On day 7, blood sam-
pad. The leg was painful and the cat ples were taken for limited haematology FIG 3. Agarose gel electrophoresis of 280 bp
was given an 8/10 lameness score. A full and biochemistry (Table 1). The only sig- amplicons derived from 14 kDa protein gene
clinical examination revealed no other nificant abnormality found was a moder- PCR. Lane 1 = Vaccinia virus strain Munich 1,
Lane 2 = Case 3, Lane 3 = Case 1, Lane 4 =
abnormalities. ate hypoalbuminaemia. Serological tests Case 4, Lane 5 = 100 bp molecular weight
Under sedation the wound was lavaged for feline immunodeficiency virus (FIV) marker, Lane 6 = Negative control (aqua test,
with saline. The cat was subcutaneously antibodies and feline leukaemia virus were no DNA)
injected with 8·75 mg/kg clavulanic negative (One Step Assay; QCR & Trio
acid-potentiated amoxycillin (Synulox; Diagnostics). On day 9, an oesophagostomy tube was
Pfizer). The treatment was then continued Treatment on days 4 to 9 consisted of: placed. On day 18, the cat was depressed
orally at a dose of 12·5 mg/kg twice daily. 11 mg/kg clindamycin (Antirobe) by and anorexic but due to tube feeding its
A single 4 mg/kg dose of carprofen mouth, twice daily; 10 mg/kg doxycycline bodyweight was unchanged. New pox
(Rimadyl; Pfizer) was given subcuta- (Ronaxan; Merial Animal Health) and 5 lesions had appeared on the trunk,
neously. mg/kg enrofloxacin (Baytril; Bayer), both although there were never more than six
The cat was presented again three days by mouth, once daily. Thereafter, the cat lesions at any time. The left foreleg was
later. It had gone missing and, therefore, was treated only with clavulanic acid- still severely swollen. There was a
had been unmedicated for two days. There potentiated amoxycillin at the doses 5  15 cm area of necrotic skin from the
was gross swelling of the entire left foreleg. previously stated, either subcutaneously point of the shoulder laterally and caudally
The soft tissue was particularly firm on the or orally. into the axilla, extending onto the flank. In

JOURNAL OF SMALL ANIMAL PRACTICE • VOL 45 • APRIL 2004 203


Godfrey 25/3/04 13:07 Page 204

Table 1. Results of haematological and biochemical tests Table 2. Comparison of the cat infections and proof of
performed on case 2 the cowpox virus infection
Normal Day 7 Day 9 Day 11 Day 18 Case 1 Case 2 Case 3 Case 4

Haematocrit 24-45% 31·5 30·4 26·4 17 Age, sex 4 y, m 4 y, f 2 y, m 1 y, m


Haemoglobin 8-15 g/dl 9·5 9·3 8·1 5·4 Main area of Lips Foreleg, Oral Forepaw,
MCHC 30-36·9 g/dl 30·2 30·6 30·9 31·8 pocks/crusts trunk mucosa, head
WBC 5-18·9  109/litre 11·8 15·9 13·1 11·6 pharynx,
Granulocytes 2·5-12·5  109/litre 8·7 11·5 10·2 7·0 tonsil
Lymphocytes/ 1·5-7·8  109/litre 3·1 4·4 2·9 4·6 A-type inclusion body + + + Negative*
monocytes (dermatohistopathology)
Platelets 175-500 170 163 281 180 Virus culture nd + nd +
Albumin 26-39 g/litre 19 21 21 21 OPXV-specific serology nd nd + (1:1024) nd
Globulin 28-51 g/litre 30 34 31 41 OPXV-specific PCR + nd + +
Total protein 57-89 g/litre 49 55 52 62
*Primary skin lesions had healed when histopathology was performed
ALT 12-130 iu/litre 43 y Years, m Male, f Female, OPXV Orthopoxvirus, nd Not determined
ALP 14-111 iu/litre 26
Urea 5·7-12·9 mmol/litre 10·3
Creatinine 71-212 µmol/litre 88
Sodium 150-165 mmol/litre 151 149 necrosis of the skin of digits II and III.
Potassium 3·5-5·8 mmol/litre 3·9 3·7
There were scattered scabs with underlying
Chloride 112-129 mmol/litre 120 122
erosions on the paw and the head. Viral
MCHC Mean corpuscular haemoglobin concentration, WBC Total white blood cell count,
ALT Alanine aminotransferase, ALP Alkaline phosphatase
culture from a scab was positive for cow-
pox virus. Cefadroxil was given at a dose of
20 mg/kg daily for three weeks and then
places this could be peeled away to reveal tion. The lamina propria had a moderate, 12·5 mg/kg clavulanic acid-potentiated
granulation tissue with exudate. The oede- lymphocyte-rich, mixed inflammatory cell amoxycillin was given orally, twice daily,
matous swelling extended from the fore- infiltrate. The lymph node biopsies had for a further four weeks.
leg to the trunk. Haematology showed a a mixed population of large and small On day 47, surgery was performed to
significant reduction in the haematocrit lymphocytes with occasional scattered remove diseased and oppose healthy tis-
(Table 1). A blood smear revealed evidence eosinophils. No follicular differentiation sues. Most of the necrotic skin had slough-
of regeneration. was recognised, probably due to the small ed and healed but digit III was completely
On day 19, the cat vomited and dis- size of the samples. lost. The foot had healed by day 60. Skin
placed the oesophagostomy tube. Because Biopsy tissue from the mouth was sub- removed on day 47 was submitted for
of the uncertain prognosis the cat was mitted for PCR testing by the method histopathology and showed furunculosis
euthanased. A postmortem examination detailed for case 1 and was positive for but no viral inclusion bodies. PCR, using
was not permitted. Orthopoxvirus. Two weeks later, serum was the technique described previously, dem-
taken for a pox antibody neutralisation test onstrated that this tissue was positive for
Case 3 using standard virus solution and vero cell cowpox virus.
A two-year-old, neutered male, domestic plates. The titre was considered to be very
shorthair cat presented in July 1999 with a high (1/1024). A small scab found on the
history of intermittent coughing and left front leg was submitted for Ortho- DISCUSSION
choking for four days. The cat was a poxvirus culture and proved negative.
known rodent hunter. No other abnormal- Oral treatment with 20 mg/kg Ideally, all cases of suspected cowpox infec-
ities were reported. Clinical examination cefadroxil (Cefa-Tabs; Fort Dodge) once tion would be confirmed by finding char-
revealed that the left submandibular daily was administered for one week. Two acteristic histopathological lesions and
lymph node was moderately enlarged. A weeks after biopsy the oral lesions were proving the presence of the virus by
total of four erosions were found in the unchanged but they had disappeared three culture, immunohistochemistry, electron
caudal mouth and over each tonsil. months after presentation. microscopy, PCR analysis or by demon-
Two wedge biopsies plus Trucut needle strating a rising antibody titre. All of the
biopsies of the lymph node were taken. Case 4 cases reported here were positive for cow-
Both oral biopsies showed ulcerative stom- A one-year-old, neutered male cat was pre- pox disease using at least two of these gen-
atitis with superficial exudates of fibrin sented in December 2001 with acute erally accepted tests (Table 2). Comparison
admixed with neutrophils. Remaining swelling of the left forepaw. It was a rodent with a 14 kDa protein (A27L) using PCR
epithelium exhibited hydropic degenera- hunter. There was no response to clavu- revealed amplificates for the three cat sam-
tion of keratinocytes and the presence of lanic acid-potentiated amoxycillin, which ples for which this test was available. So far,
abundant hyaline, eosinophilic, intra- was given orally at a dose of 12·5 mg/kg more than 100 Orthopoxvirus strains and
cytoplasmic inclusion bodies, consistent twice daily for five days, and 0·1 mg/kg isolates have been successfully amplified
with poxvirus inclusions. In one of the meloxicam (Metacam; Boehringer Ingel- with this PCR (H. Meyer, unpublished
biopsy samples there was also marked, heim) given orally with food daily. Five data). In this small case series, finding
mainly lymphocytic, superficial inflamma- days later the cat was re-presented with pathognomonic A-type inclusions on der-

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Godfrey 25/3/04 13:07 Page 205

matohistopathology was useful and is a rel- previously reported in cats with extensive infection. Journal of Small Animal Practice 31, 167-
173
atively rapid diagnostic technique. In con- cowpox disease associated with FIV (Brown BENNETT, M., HAZEL, S., BEGON, M. & BAXBY, D. (1999)
junction with PCR, these four unusual and others 1989, Hübner 2002). Such Cowpox in cats (and mice and men). Proceedings of
the British Veterinary Dermatology Study Group.
cases could be clearly diagnosed. extensive skin lesions and oedema caused October 1999. pp 5-9
All four cats were typical candidates for by cowpox virus is not reported in the lit- BROWN, A., BENNETT, M. & GASKELL, C. J. (1989) Fatal
poxvirus infection in association with FIV infection.
cowpox infections as they lived in rural erature. Veterinary Record 124, 19-20
CHANTREY, J., MEYER, H., BAXBY, D., BEGON, M., BOWN,
locations and were active hunters of Case 4 was worth reporting because the K. J., HAZEL, S. M., JONES, T., MONTGOMERY, W. I. &
rodents. Three cases presented between literature does not state that cowpox can BENNETT, M. (1999) Cowpox: reservoir hosts and
geographic range. Epidemiology and Infections
May and August, the low season for the cause such severe deformation. The initial 122, 455-460
disease in the UK (Bennett and others differential diagnoses considered were bac- ESSBAUER, S., MEYER, H., KAADEN, O-R. & PFEFFER, M.
(2002) Recent cases in the German poxvirus con-
1999). The reason for this is unknown. terial and fungal infections, vasculitis, sular laboratory. Revue de Medecine Veterinaire
Case 1 was unusual in that the skin disease envenomation, neoplasia, blunt trauma 153, 635-642
HARGIS, A. M. & GINN, P. E. (1999) Feline herpesvirus 1-
was confined to ulceration of the oral and thermal damage. associated facial and nasal dermatitis and stomati-
mucocutaneous junction. Case 3 was tis in domestic cats. Veterinary Clinics of North
America: Small Animal Practice 29, 1281-1290
unusual in that oral lesions were found Conclusions HAZEL, S. M., BENNETT, M., CHANTREY, J., BROWN, J.,
without skin lesions. Oral disease in the These four cases of cowpox in cats demon- CAVANAGH, R. & JONES, T. R. (2000) A longitudinal
study of an endemic disease in its wildlife reservoir:
absence of skin disease has not previously strate the need to consider cowpox virus as cowpox and wild rodents. Epidemiology and Infection
been reported. More usual differential a potential cause of a range of clinical pre- 124, 551-562
HINRICHS, U., VAN DE POEL, H. & VAN DEN INGH, T. S. G. A. M.
diagnoses for cases 1 and 3 would be aller- sentations. Cowpox lesions may be hid- (1999) Necrotizing pneumonia in a cat caused by an
gic or contact irritant diseases, eosinophilic den, as in case 3, and oedema can be a orthopox virus. Journal of Comparative Pathology
121, 191-196
granuloma complex, bacterial infections, prominent sign. Seasonality is an unreli- HÜBNER, J. (2002) Katzenpockeninfektion in Deutsch-
autoimmune and neoplastic diseases, able factor (Pfeffer and others 2002). The land. Ein fallbericht. Tierärztlich Praxis 30, 442-444
KAPLAN, C., HEALING, T. D., EVANS, N., HEALING, L. & PRIOR,
FIV, herpesvirus or calicivirus infections only common feature is that affected cats A. (1980) Evidence of infection by viruses in small
(Hargis and Ginn 1999, Stokes and others are rodent hunters. Therefore, veterinary British field rodents. Journal of Hygiene (London) 84,
285-294
1999, Thiel and Konig 1999). surgeons should always enquire about a MARENNIKOVA, S. S., LADNYJ, I. D., OGORODINIKOVA, Z. I.,
Cats presenting with lesions similar cat’s hunting habits when taking a clinical SHELUKHINA, E. M. & MALTSEVA, N. N. (1978) Identifi-
cation and study of a poxvirus isolated from wild
to those of case 2 have differential diagnoses history. rodents in Turkmenia. Archives of Virology 56, 7-14
of trauma, allergic oedema, bacterial infec- MEYER, H., PFEFFER, M. & RZIHA, H. J. (1994) Sequence
alterations within and downstream of the A-type
tions, neoplasia and obstructive oedema. A Acknowledgements inclusion protein genes allow differentiation of
similar presentation has recently been Poxvirus cultures and poxvirus serology Orthopoxvirus species by polymerase chain reaction.
Journal of General Virology 75, 1975-1981
reported with a novel virulent feline cali- were performed at the clinical pathology PEDERSEN, N. C., ELLIOTT, J. B., GLASGOW, A., POLAND, A. &
civirus (Pedersen and others 2000). The rea- diagnostic service, at the Department of KEEL, K. (2000) An isolated epizootic of hemorr-
hagic-like fever in cats caused by a novel and
son for case 2 failing to recover is unknown. Clinical Veterinary Science, University of highly virulent strain of feline calicivirus. Veterinary
The animal was apparently healthy prior to Bristol. The authors would like to thank Microbiology 73, 281-300
PFEFFER, M., PFLEGHAAR, S., VON BOMHARD, D., KAADER, O-R.
the cowpox infection but an additional those involved. & MEYER, H. (2002) Retrospective investigation of
immunosuppressive disease could not be feline cowpox in Germany. Veterinary Record 150,
50-51
ruled out. Use of in-house biochemistry and References STOKES, C. R., FINERTY, S., GRUFFYDD-JONES, T. J., STURGESS,
BAXBY, D. & BENNETT, M. (1997) Cowpox: a re-evaluation C. P. & HARBOUR, D. A. (1999) Mucosal infection and
haematology analysers is not ideal. The of the risks of human infection based on new epi- vaccination against feline immunodeficiency virus.
hypoalbuminaemia was thought to be demiological information. Archives in Virology Journal of Biotechnology 73, 213-221
(Supplement) 13, 1-12 THIEL, H. J. & KONIG, M. (1999) Caliciviruses: an
secondary to loss of albumin into the oede- BAXBY, D., BENNETT, M. & GETTY, B. (1994) Human cow- overview. Veterinary Microbiology 69, 55-62
matous tissue. The anaemia was not investi- pox; a review based on 54 cases, 1969-93. British WOLFS, T. F., WAGENAAR, J. A., NIESTERS, H. G. & OSTERHAUS,
Journal of Dermatology 131, 598-607 A. D. (2002) Rat-to-human transmission of cowpox
gated because the cat was euthanased. BENNETT, M., GASKELL, C. J., BAXBY, D., GASKELL, R. M., infection. Emerging Infectious Diseases 8, 1495-
Anaemia and hypoalbuminaemia have been KELLY, D. F. & NADOO, J. (1990) Feline cowpox virus 1496

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