REVIEW ARTICLE

A Case of Facial Cellulitis and Necrotizing

Lymphadenitis due to Cowpox Virus Infection
Roland Pahlitzsch,1 Anna-Lena Hammarin,2 and Anders Widell3
1

Department of Otolaryngology, Blekinge County Hospital, Karlskrona, 2Department of Virology, Swedish Institute of Infectious Disease Control,
Stockholm, and 3Department of Medical Microbiology, Malmo University Hospital, Lund University, Malmo, Sweden

Facial infection of the skin and soft tissues can be due

to a number of bacterial agents, but it can also be due
to viruses such as herpes simplex virus type 1, varicella
zoster virus, and a range of poxviruses. Formerly, variola virus had humans as its exclusive host, but with
its eradication through mass vaccination, the total
number of poxvirus infections has been dramatically
reduced. However, cases of zoonotic poxvirus infection
have occasionally involved humans. Such cases may
present diagnostic difficulties and may have devastating
outcomes [1]. We report a case of cowpox infection
with a prolonged disease course, and we discuss the
viral, diagnostic, epidemiological, and therapeutic
aspects.
CASE REPORT
In early November 2000, a 7-year-old girl living in the
southeast of Sweden sought medical attention from a

Received 28 February 2006; accepted 23 May 2006; electronically published 10

August 2006.
Reprints or correspondence: Dr. Roland Pahlitzsch, Dept. of Otolaryngology,
Blekinge County Hospital, S-37185, Karlskrona, Sweden (roland.pahlitzsch
@ltblekinge.se).
Clinical Infectious Diseases 2006; 43:73742
 2006 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2006/4306-0012$15.00

general practitioner. She presented with an inflammatory, erythematous swelling of the skin beneath the
right ear and painless lymphadenopathy in the regional
parotid and upper jugular lymph nodes. She had no
history of skin injury in the affected region of the head
and neck. Two weeks before the onset of symptoms,
the patient had visited Spain. She had received childhood vaccinations against mumps, rubella, measles, poliomyelitis, Haemophilus influenzae, and diphtheria-tetanus-pertussis, but she had not received vaccination
against tuberculosis or smallpox. There was no history
of immunodeficiency or atopia.
The patient had a low-grade fever (temperature,
38C) and general malaise, and because a bacterial
infection was suspected, she was treated orally with
penicillin. Despite the administration of treatment, the
symptoms progressed, and the patient was referred to
the Department of Otolaryngology at Blekinge County
Hospital (Karlskrona, Sweden) on 26 November 2000.
Three weeks after the onset of the first symptoms, her
condition worsened. Extensive edema developed in the
upper part of the right side of the neck and on the
right side of the face, extending into the contralateral
side and involving the eyelids; it also developed on the
mental region and the upper part of the right side of
the neck (figure 1A and 1C).
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We describe a patient with facial cellulitis/erysipelas due to cowpox virus inoculation in the respiratory
epithelium of the nose. A cytopathic agent was isolated in cell culture, and the diagnosis of cowpox was
confirmed by electron microscopy and polymerase chain reaction. The most likely source of infection was
exposure to the family cats. In addition to the severe edematous cellulitis of the face, the clinical course was
dominated by several areas of subcutaneous, necrotizing lymphadenitis, from one of which a huge abscess
formed that had to be incised. Hyperbaric oxygen treatment was provided to prevent development of dermal
necrosis. The healing process in the numerous areas of lymphadenitis was markedly protracted, and 1 persisting
node (which yielded positive results on polymerase chain reaction) had to be excised 2 years after onset of
disease. This is the first reported case of inoculation of cowpox virus in the respiratory mucosa of the nose.
It resulted in a clinical course totally different than that for inoculation in the skin. We also present a short
review of findings on orthopoxvirus infection that focuses on the chain of transmission.

Physical examination was performed at the time of hospital

admission and revealed a whitish, necrotizing mass in the right
anterior nasal cavity that was surrounded by granulations at
the anterior border of the lower nasal concha. Numerous solid
lymph nodes (diameter, 325 mm) were palpable in the right
cheek, near the right nostril, near the right eye (including the
upper eyelid), and more laterally, anterior to the border of the
right parotid gland.
The WBC count (11.3 10 9 cells/L) was nearly normal (normal WBC count, !9.6 10 9 cells/L). Other laboratory values
were slightly elevated: the C-reactive protein level was 14 mg/
mL (normal level, !5 mg/mL), the serum alkaline phosphatase
level was 7.9 mkat/L (normal range, 1.04.5 mkat/L), and the
lactate dehydrogenase level was 9.3 mkat/L (normal range, 3.0
7.0 mkat/L). Plasma electrophoresis revealed a slightly raised
level of IgG3 (1.4 g/L; reference values, 0.131.05 g/L), but the
findings were otherwise normal.
Bacteriologic study findings. A nasal swab culture yielded
Streptococcus mitis (low numbers), Haemophilus parainfluenzae
(low numbers), and Neisseria species, including 1 oxidase pos738 CID 2006:43 (15 September) Pahlitzsch et al.

itive rod-like bacterium. Samples were obtained for Mycobacterium tuberculosis culture, and the results were negative.
The overall interpretation was that the local skin infection
was a phlegmon caused by H. influenzae (although culture results were negative). Treatment with intravenous cefuroxime
was started on a tentative basis.
Histologic study findings. Biopsy from the nose mass revealed necrotic material with granulocytes.
Radiographic study findings. CT revealed deep edema of
the right cheek, the right parotid gland, and the right side of
the neck. Edema of the respiratory epithelium of the anterior
ethmoidal cells and the nasal concha on the right side could
also be visualized (figure 1B).
Subsequent clinical course. One week after the acute exacerbation a slight improvement of the cellulitis under the eye
occurred. Around the areas of facial lymphadenitis the skin still
showed a bluish discoloration. However, since the patients
general condition improved, she was discharged from the hospital and followed up on weekly visits to our outpatient clinic.
The cellulitis completely resolved within 3 weeks after onset,

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Figure 1. Serial photographs and a CT scan for a patient with facial cowpoxvirus infection. A, Lesion and facial edema 2 weeks after onset of
infection. B, CT obtained 2 weeks after onset. C, Abscess prior to hyperbaric oxygen treatment and surgical incision 6 weeks after onset. D, Status
4 months after hyperbaric oxygen treatment and incision. E, Close-up of long-lasting lesion in medial canthus 24 month after onset. F, Late results,
36 months after onset, showing a minimum of scarring. G, Electron microscopic image of orthopoxvirus obtained from our patient. Consent to appear
in the photographs was obtained from the patients guardian.

ysis, which noted a 339-bp fragment of the viral thymidine

kinase gene, where direct sequencing revealed 100% homology
with an earlier published Swedish isolate, H2 [2]; direct sequencing also revealed, as expected, 99% homology with vaccinia virus sequences. A serum sample, which had been collected 5 weeks after the onset of symptoms, was positive for
antibodies to orthopoxvirus (vaccinia virus) by plaque reduction neutralization test.
The healing process of the numerous areas of lymphadenitis
was markedly prolonged. Two years after onset of symptoms,
a single firm node situated in the medial angulus of the right
eye was removed (figure 1E). Electron microscopy evaluation
of this node yielded negative results, but PCR of the node was
positive for orthopoxvirus DNA. Sequence analysis showed total homology with the PCR product obtained from the patient
in February 2001.
Epidemiological findings. After cowpox infection was diagnosed (almost 3 months after the onset of symptoms), the
patient recalled having had close contact with 2 domestic cats.
One of the cats used to lick her face and nose. Close contact
with the cats was especially frequent after she came home from
the holiday in Spain. On this occasion, the cats tongue penetrated the right nasal cavity; 2 weeks later, the first symptoms
appeared. No scratches were found on the girls nose. The cats
were in good health when examined by a veterinarian in February 2001. None of them had lesions of the paws, mouth, or
nose or enlarged lymph nodes of the neck. Serum samples
obtained from both cats were tested for orthopox virus antibodies at the Swedish Veterinary Institute (Uppsala), and the
results were negative.
DISCUSSION
Poxviruses are the largest enveloped DNA viruses, with an average dimension of 230 300 nm. The virus particle contains
a linear, double-stranded genome of 140300 kb in length that
encodes several hundred polypeptides. Vertebrate poxviruses
contain 8 genera, of which 4 (Orthopoxvirus, Parapoxvirus,
Yatapoxvirus, and Molluscipoxvirus) contain viruses pathogenic to humans [3], all of which, with the exception of smallpox (variola), vaccinia virus, and molluscipoxvirus, are transmitted to humans by animals (zoonosis).
Smallpox was caused by the variola virus, a member of the
Orthopoxvirus genus. It was globally eradicated in the late
1970s by mass vaccination, which was successful, because the
variola virus did not have an animal reservoir. Vaccinia, known
as the Jenner virus, was the virus used for successful smallpox
vaccination, but the exact origin of vaccinia virus is uncertain
and there is no known natural host.
Vaccination with vaccinia virus provided cross-protection
against several orthopoxviruses, including monkeypoxvirus, the
third orthopoxvirus. Normally, vaccinia causes mild and local

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but the lymphadenitis in the buccal and periorbital areas developed into subcutaneous abscess cavities, which ranged in
size from 3 to 40 mm. The largest of these abscess cavities
measured 40 25 mm and extended from the paranasal region
into the right cheek (figure 1D). The subcutaneous fat layer at
the site of the abscess cavity underwent a complete necrosis.
Repeated needle punctures produced a whitish, smeary discharge, a specimen of which was sent for general and specific
bacterial culture and, subsequently, for virus isolation on 19
December 2000.
Approximately 6 weeks after the onset of symptoms, the
dermis in the region of the paranasal abscess became extremely
thin and was at risk of necrosis and perforation. Three punctuations, which were made under general anesthesia during an
interval of 35 days, had no effect on the condition, and incision became inevitable. Because of the risk of dermal necrosis,
hyperbaric oxygen (HBO) treatment was chosen as therapy, to
improve the chances that the infection would resolve and to
stabilize the atrophied skin before incision. The patient underwent 5 courses of HBO treatments, in 6 hourly intervals,
between the 21st and the 23rd of December in the pressure
chamber at the Karlskrona Naval Base.
After the first course of HBO treatment, the huge paranasal
abscess was evacuated by incision, and a drain was inserted.
The discharge diminished gradually, and the drain was removed
after 5 days. The patients condition quickly improved, and 6
weeks after she underwent HBO therapy and the incision, the
skin had recovered completely, including a reappearance of the
subcutaneous fat layer. However, some lymph nodes continued
to vary in size, and the bluish discoloration of the adjacent skin
areas remained. Nodes of 23 mm in diameter in general
showed spontaneous regression, but nodes with a diameter of
515 mm required needle aspirations several times, for up to
5 months after the onset of the disease. Histologic examination
of the discharge showed degenerated hyperplastic unidentifiable
cells. Examination of fine-needle biopsy specimens from the
upper jugular lymph nodes, which never necrotized, revealed
reactive lymphadenitis.
The aspirate obtained on 19 December was subjected to virus
isolation at the Department of Virology at Malmo University
Hospital (Malmo, Sweden). Ten days after inoculation on
green-monkey kidney cells, a cytopathic effect (CPE) appeared,
which, on subpassage, yielded syncytial formation of the cells.
The CPE was caused by an agent that was filterable through a
0.45-mm filter. The results of PCR and immunofluorescence
testing for mumps virus were negative.
The CPE pattern directed our suspicions to poxvirus infection, and the culture material was sent to the Swedish Institute
for Infectious Disease Control in Stockholm on 9 February 2001
for investigation for poxvirus. Orthopoxvirus-like particles
were detected in the culture medium by electron microscopy
(figure 1G). The diagnosis was further confirmed by PCR anal-

Table 1.

illary lesions from the growth of virus in the endothelial and

pericapillary cells [14].
The lesion is usually painless, as was true for our patient,
who never complained of any pain in her nose. The lesion may
be located on the skin or mucosa, and it is typically surrounded
by marked local edema and regional lymphadenopathy, which
may be prolonged, as it was in our case. Furthermore, most of
the reported patients have slight systemic symptoms, such as
pyrexia, and they sometimes experience sore throat, influenzalike illness, and general malaise that lasts 310 days. The time
to complete recovery ranges from 3 to 12 weeks and can be
even longer. A selection of reported clinical features is presented
in table 2 [1523].
Our patient had a hitherto undescribed route of inoculation
via the respiratory mucosa of the nose. The infection resulted
in a mucosal inflammation that resolved after 3 weeks. We
found necrotic material at the site of the inferior concha that
was surrounded by pebble stone-like granulations. The subsequent phase was dominated by subcutaneous necrotizing
lymphadenopathy of the regional nodes; this persisted for several months and required therapeutic needle aspirations.
The major abscess in the paranasal region covered by an
extremely thin dermis was at risk of necrosis, and the unorthodox decision was made to support surgical treatment with
HBO treatment. Several clinical and experimental studies have
demonstrated the usefulness of HBO treatment (e.g., the beneficial effect on stimulation of granulocytes and on circulation)
[24, 25]. There was a strong clinical impression that HBO treatment had a beneficial effect on the healing process (figure 1D
and 1F). Incision of the large abscess and placement of a temporary drain were also important; however, several evacuating
punctures had been performed earlier while the patients condition had continued to deteriorate.
Diagnosis was delayed for our patient, because the initial

Reports on spread of orthopoxvirus in western European rodents and carnivores.

Country
Great Britain

Mode of detection

Reservoir

Serologic testing and PCR

Bank voles (prevalence in autumn, 80%), wood mice (prevalence, 27%),

and short-tailed field voles (Clethrionomys glareolus, Apodemus sylvaticus,
and Microtus agrestis; prevalence, 99% [11 of 12])
Cats (prevalence, 2% [44 of 2173])

Germany

Serologic testing

Norway

Serologic testing

Finland

Serologic testing and PCR

Reference(s)
[57]

[8]

Wild carnivores (red foxes [Vulpes vulpes]; prevalence, 11% [7 of 62]) and domestic cats (prevalence, 10.1% [n p 217])
Rodents (mainly bank voles [Clethrionomys glareolus]; prevalence, 0%92%,
depending on population dynamics; high prevalence during the peak phase
of population for red foxes (prevalence, 50% [7 of 14]) and lynx (prevalence, 1.4% [1 of 73])

[9]
[10]

Sweden

Serologic testing

Lynx (prevalence, 29%; [5 of 17]) and brown bears (prevalence, 2%; [1 of 45])

[10]

Germany

Serologic testing

Red foxes (prevalence, 6.5% [46 of 703])

[11]

Austria

Serologic testing

Domestic cats (prevalence, 4% [(8 of 200])

[12]

740 CID 2006:43 (15 September) Pahlitzsch et al.

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symptoms, but it may cause severe and even fatal complications

in immunocompromised individuals [1].
Monkeypoxvirus acquired attention in 19691970, when it
was isolated from infected humans in Congo/Zaire. Increasing
numbers of human monkeypox infections have been observed
in later years in this region of Africa, where infection occurs
in the wildlife [4].
Cowpoxvirus, the fourth orthopoxvirusand the causative
agent of our caseis so named because it can infect the teats
of cows [2]. However, despite its name, cowpoxvirus does not
have cattle as its reservoir host; rather, rodents (such as bank
voles and wood mice) serve as its reservoir hosts [5, 6]. Carnivore hosts (such as cats) that hunt rodents can transmit cowpoxvirus to humans. Serological investigations have recognized
domestic cats as the most common hosts for cowpoxvirus [7].
Antibodies against orthopoxvirus have been documented in
several rodents and carnivores; the species are shown in table
1 and are described elsewhere [512].
In our case, the domestic cats did not show any signs of
ongoing infection on examination, although the examination
was not performed until 3 months after exposure. Also, serological investigation (immunofluorescent staining) did not
reveal antibodies to orthopoxvirus.
Human cowpoxvirus infection is a rare disease. A review of
54 cases, most of which were in the United Kingdom, indicated
that human cases coincided with autumn peaks of cowpoxvirus
infections in voles, wood mice, and domestic cats [13]. In most
of the cases involving humans, the source of the infection is
domestic cats. The infection is almost always transferred to
humans through a skin lesion, but in some cases, it is transferred via the mucosa of the eye. Infection usually starts as an
inflamed macula that turns into a papule; finally, a vesicular
stage occurs within 712 days. The dermal vesicles become pale
blue-purple and are more or less hemorrhagic, because of cap-

Table 2.

Clinical manifestations in a selection of reported cases of cowpox.

Country

Year

Source

Germany

1990

Homeless, ill cat

Germany

1996

Germany

Age,
years/sex of
human patients

Outcome

18/M

Skin; generalization; possible lung

involvement

Immunocompromised patient
died of thromboembolism

[15]

Hunting cat

11/F

Neck; ulceration and regional

lymphadenitis

Recovery after 8 weeks

[16]

2000

Hunting cat

11/M

Cheek; skin blister and regional

lymphadenitis

Recovery after 2 months

[17]

Germany

2003

Cat

36/M

Eyebrow; skin blister and regional lymphadenitis

Recovery within 3 weeks

[18]

France

2004

Cat

11/M

Sacrum; wound; cutaneous and

mucous membrane lesions

Slow recovery

[19]

Great Britain

1996

Healthy dog

41/M

Nasal tip; ulcer after scratch; bilateral cervical lymphadenitis

Recovery after 6 months

[20]

Sweden

1990

Hunting cat

12/F

Neck and skin blisters; regional

lymphadenitis

Recovery after 6 weeks

[21]

Sweden

1990

Hunting cat

14/F

Conjunctivitis; regional
lymphadenopathy

Recovery after 2 months

[21]

The Netherlands

2002

Wild rat (Rattus norvegicus)

14/F

Eyelid; ulceration and regional

lymphadenitis

Recovery after 1 month

[22]

Austria

2003

Cat (possibly hunting)

56/F

Neck, ulceration (possible

lymphadenopathy)

Recovery after 5 weeks

[23]

Finland

2003

Patients dog

Extremities, body, face, vulva;

generalization of atopic
dermatitis

Recovery after 2 months

[10]

4/F

massive cellulitis of the face resembled a H. influenzae phlegmon; however, the results of cultures were negative. There were
few indications pointing to a virus infection, and unfortunately,
the biopsy specimen from the nose was not sent for virological
analysis. Virus isolation from the discharge obtained 3 weeks
after hospital admission yielded a syncytium-like pattern that
was confirmed to be orthopoxvirus by electron microscopy and
was eventually verified as cowpoxvirus by PCR and sequencing.
Although it would have been desirable to test tissue specimens
for specific viral antigens, no such tests were performed, because
the poxvirus particles and DNA that were present were unlikely
to be contaminants in an unvaccinated child. Furthermore,
examination by PCR and restriction digest performed at the
Centers for Disease Control and Prevention (Atlanta, GA) confirmed that the virus isolate was cowpox species.
Antibiotics (penicillin, cefuroxime, and spectramycin) were
prescribed to our patient on the basis of sparse findings of
bacterial infection and to prevent secondary infection at the
sites for puncture and incision. This therapy had no convincing
effect on the course of the disease.
At the time of diagnosis, antiviral treatment was considered.
Cidofovir is efficient against vaccinia virus infections in mice,
although it has been associated with some renal toxicity in
humans [26]. Of the other treatment options, immune globulin
was considered, as was vaccination with vaccinia virus. How-

Reference

ever, by this point in the course of infection, most of the symptoms had decreased, except persisting lymphadenopathy.
Most reported cases of cowpox in humans who are infected
via cats involve girls aged 12 years [17]. A tendency among
girls in this age group to cuddle cats, as in our patient, may
explain this phenomenon. Unfortunately, the patient never told
us that her cat licked her nose until we asked.
In most of the cases, the patient presents with a necrotizing
skin lesion or may have a blister with involvement of the regional lymph nodes. However, if the virus has been inoculated
via a mucosal membrane (such as the eye [21] or, as occurred
in our patient, the nasal mucosa), the result may be massive
facial edema resembling erysipelas linked with lymphadenopathy. In such atypical cases, animal contacts and cowpoxvirus
infection should be ruled out.
Whether the abolition of smallpox vaccination in Europe
during 19711977 has led to an increase in the number of
cowpoxvirus infections is still a matter of discussion. During
the period of 19821993, Baxby et al. [13] reported 25 cases
after cessation of vaccination in 1971 in Great Britain, as well
as 20 cases during 19691981. Sweden reported 2 cases in 1990;
there has also been our case in 2000 and a still unreported case
in 2005. Despite a growing awareness of human cowpox infection in Europe, diagnosis is certainly often missed because
cowpox infection may resemble impetigo, anthrax, or erysip-

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Cowpox manifestation

10.

Acknowledgments

11.

We are thankful for fruitful discussions with Dr. Henning Montelius

(Department of Infectious Diseases, Blekinge County Hospital, Karlskrona,
Sweden) and Dr. Nils Hamnerius (Department of Dermatology, Blekinge
County Hospital). We also thank Dr. Johan Douglas (Department of Anaesthesia) for administering effective hyperbaric oxygen therapy and Dr.
David Allen (Department of Anaesthesia) for revising the English language
test in this manuscript. We thank colleagues at the Department of Ear,
Nose, and Throat (Blekinge County Hospital; Karlskrona, Sweden) for
taking part in the surgical procedures. We also acknowledge the input of
Dr. Monica Grandien, Dr. Fredrik Elgh, and Dr. Kari Johansen (Virology
Department, Swedish Institute for Infectious Disease Control, Stockholm)
for critically reviewing the manuscript and Dr. Kjell Olof Hedlund (Virology
Department, Swedish Institute for Infectious Disease Control, Stockholm)
for performing electron microscopy.
Financial support. ALF grants from the Medical Faculty of Lund
University.
Potential conflicts of interest. All authors: no conflicts.

12.

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elas; moreover, the disease often heals spontaneously within 4

6 weeks. It is possible that only the more spectacular cases are
reported, making it difficult to estimate any increase in the rate
of human cases of cowpox after cessation of vaccination.