a case of feline phaeohyphomycosis due to fonsecaea pedrosoi (pages 297–301)
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Veterinary Dermatology2001, 12, 297301
BlackwellScience,Ltd
Case report
A case of feline phaeohyphomycosis due toFonsecaea pedrosoi
ALESSANDRA FONDATI,* MARIA GRAZIA GALLO, ERICA ROMANO and
DOLORES FONDEVILA*
*Facultat de Veterinria, Universitat Autnoma de Barcelona, Barcelona, Spain;
Facolt di Medicina Veterinaria, Universit degli Studi di Torino, Torino, Italy;
Private Practitioner, Rome, Italy
(Received9 May2000; accepted13 March2001)
Abstract The first report of a case of feline phaeohyphomycosis due to Fonsecaea pedrosoiis presented.
Fonsecaea pedrosoiis an aetiologic agent of both human phaeohyphomycosis and chromoblastomycosis. In our
cat, the lesion was confined to the skin and appeared as a firm swelling on the bridge of the nose. Diagnosis was
based on histological examination of a cutaneous biopsy and fungal culture of a tissue sample on Sabourauds
dextrose agar. Further diagnostic tests failed to reveal an underlying immunosuppression. Two treatment cycles
with itraconazole, at the oral dose of 5 mg kg1given twice daily, induced complete clinical remission, but
relapses occurred.
Keywords:cat, Fonsecaea pedrosoi, mycosis, phaeohyphomycosis.
INTRODUCTION
Phaeohyphomycosis is an infection of animals andhumans caused by dematiaceous fungi. Dematiaceous
fungi are defined as those that have melanin or
melanin-like pigment in their cell walls.1They are a
heterogeneous group of organisms unified by their pro-
duction of melanin pigments. In phaeohyphomycosis
these fungi develop in the host tissues in the form of
dark-walled dematiaceous septate mycelial elements.2
The dematiaceous elements, in tissue, appear as either
irregularly septate hyphae, branched or unbranched,
or as yeast-like cells, solitary or in short chains.
Fourteen different fungal species belonging to 12
genera
3
have been documented as agents of felinephaeohyphomycosis and include, among others,
Alternaria sp., Cladophialophora sp., Curvularia sp.,
Drechslera sp., Exophiala sp., Moniliella sp., Ochro-
conis sp., Phialophora sp., Scolecobasidium sp. and
Stemphyliumsp. These fungi are found widely in nature
and live ubiquitously in soil, usually associated with
plant material. Traumatic implantation of fungal
elements leads to chronic granulomatous infection of
viable cutaneous tissues. Variably ulcerated nodules
develop most commonly on the face and distal extre-
mities. Systemic spreading of fungal elements is rare.
This report describes a case of phaeohyphomycosis
due to Fonsecaea pedrosoiin a cat. To our knowledge
this is the first description of feline phaeohyphomycosisdue to F. pedrosoi.
CASE REPORT
A 4-year-old, neutered male, Domestic Long Hair cat was
presented with a 7-month history of a progressive, non-
pruritic swelling on the bridge of the nose accompanied
by sneezing. The owner explained that the swelling
initially had a black dot on the surface and that a pre-
sumptive wasp sting preceded it by a few weeks. The cat
had been treated unsuccessfully with systemic antibiotics.At dermatological examination, a firm and hard
swelling was present on the bridge of the nose. The
swelling was nonpainful on palpation and the over-
lying skin was normal (Fig. 1). At physical examination
the cat was otherwise healthy.
Differential diagnosis included eosinophilic granu-
loma, foreign body reaction, deep fungal and/or
bacterial infection and neoplasia. The diagnostic plan
included fine-needle aspiration cytology and cutaneous
biopsy and, depending on the results, further mycolo-
gical and bacteriological cultures, haematological, bio-
chemical, serological and radiographic evaluations.
Cytological examination of air-dried preparations stainedwith Diff-Quik revealed degenerated neutrophils
and macrophages. Histological examination of haema-
toxylin and eosin (H&E)-stained sections revealed a
Correspondence: Alessandra Fondati, Facultat de Veterinria,
Universitat Autnoma de Barcelona, 08193 Bellaterra; Barcelona,
Spain. Tel.: +34 93 5811421, Fax: +34 93 5813142, E-mail:
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dermal nodule consisting of an accumulation of
macrophages, neutrophils, plasma cells and lymphocytes
surrounding brown-pigmented and thick-walled fungal
yeast-like cells and hyphae. Hyphae appeared branched
and closely septate (Fig. 2). Multinucleated giant
cells were also present. Inflammatory cells were pre-
sent in the surgical margins. On tissue sections, fungal
elements stained strongly with periodic acid Schiff
(PAS) (Fig. 3) and Gomoris methenamine silver
(GMS) stains. The histopathological diagnosis waspyogranuloma due to dematiaceous fungi. Based on
the clinicalpathological findings the diagnosis was
phaeohyphomycosis.
Further diagnostic evaluation was performed to rule
out underlying systemic diseases, immunosuppression
and deep fungal invasion. Both complete blood count
and serum chemistry profile were within normal limits
for the reference laboratory. Enzyme-linked immuno-
assays (ELISAs) to detect feline leukaemia viral antigen
and antibody to feline immunodeficiency virus were
negative. Nasal, thoracic and abdominal radiographs
did not show abnormalities.
Fungal cultures of cutaneous tissue specimens wereperformed to identify fungal organisms. The epidermis
was removed from a cutaneous biopsy specimen, the
sample was then ground aseptically, placed in sterile
saline and the suspension was used to inoculate
Sabourauds dextrose agar plates. The organism was
identified as F. pedrosoiin the Department of Animal
Production, Ecology and Epidemiology, Faculty of
Veterinary, Turin (Prof. M.G. Gallo), where it is depos-
ited in a mycological collection.
Cultures gave rise in 3 weeks to velvety, dark olive
green colonies with shallow radial grooves (Fig. 4).
The colony reverse was deep black. Because of great
colonial variation within the species F. pedrosoi, fungalidentification was obtained through microscopic exam-
ination of conidia (Fig. 5). Microscopically, conidial
structures of both Rhinocladiella (acropleurogenus)
and Cladosporiumtypes were observed. The Rhinocla-
diellatype of conidia was characterized by sympodial
conidiophores bearing brown, single-celled, oval
conidia in their upper portion. The conidia were pro-
duced on short denticles. Some conidia produced
secondary conidia. This represents a salient feature to
differentiate the genus Fonsecaeafrom Rhinocladiella,
which produces a single row of conidia around a conid-
iophore. The Cladosporiumtype of conidia was char-
acterized by very short conidial chains obtained byprogressive budding, as observed in the genus
Cladosporium. Moreover, flask-shaped phialides pro-
vided by distinctive collarettes, typical of the genus
Figure 1. Feline phaeohyphomycosis due to Fonsecaea pedrosoi.
Swelling on the bridge of the nose. Photo reproduced from A
Practical Guide to Dermatology, 1999 Merial.
Figure 2. Histopathology. Brown-pigmented, thick-walled yeast-
like fungal cells (arrowhead) and irregularly septate hyphae (arrow)
surrounded by macrophages, neutrophils, plasma cells andlymphocytes (H&E 400).
Figure 3. Histopathology. Numerous, slightly brown-pigmented,
periodic acid Schiff (PAS)-positive fungal elements (PAS 400).
Figure 4. A velvety, olive green fungal colony of Fonsecaea pedrosoi
cultured on Sabourauds dextrose agar.
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Phaeohyphomycosis in a cat 299
Phialophora, were observed (Fig. 6). All these features
are reported as characteristic of F. pedrosoi.4 6
Because of the anatomical site, complete resection of
the lesion was considered unlikely, and therefore anti-
fungal chemotherapy was preferred. The cat was
treated with oral itraconazole at a dosage of 5 mg kg1
given twice a day. A complete response to therapy was
observed with return to clinical normality in 1 month.
Itraconazole therapy was well-tolerated and was main-
tained for a further 3 months. Six months after the ini-
tial treatment was withdrawn a relapse occurred and
itraconazole therapy was reinstated at the same dosage.
Complete clinical remission was obtained in 1 month
and therapy was maintained for a further 5 months. A
second relapse was observed 9 months after therapywithdrawal. Unfortunately, at this time, the cat was lost
to follow-up.
DISCUSSION
Dematiaceous fungi may cause phaeohyphomycosis,
black-grain eumycotic mycetoma and chromoblasto-
mycosis.1Phaeohyphomycosis is an uncommon infec-
tion in European countries and occurs more frequently
in tropical and subtropical regions. However, cases
of feline and human phaeohyphomycosis have beenrecorded in Europe.1,3,7 Phaeohyphomycosis is an
ever-increasing presence in human disease and, as the
population of immunocompromised patients con-
tinues to grow, the incidence of phaeohyphomycosis,
particularly the disseminated disease, will most likely
continue to increase.8Over the years, the list of fungi
causing human phaeohyphomycosis has grown con-
siderably and will likely continue to expand. Feline
subcutaneous phaeohyphomycosis is not usually asso-
ciated with immunosuppression and the number of
cases recorded remains relatively low. 3,9Nevertheless,
the list of fungi causing feline phaeohyphomycosis has
also grown in recent years.Black-grain eumycotic mycetomas are characterized
clinically by the triad of tumefaction, draining sinuses
and the presence of brown granules in the discharge
from sinuses.10Examination of granules reveals struc-
tures that vary, depending on the fungus, from ones
composed of septate, branching hyphae to those con-
sisting of a compact mass of rounded cells. Curvularia
sp. and Phaeococcus sp.9have been isolated in feline
black-grain eumycotic mycetomas.
Chromoblastomycosis is a chronic cutaneous and
subcutaneous infection characterized by the presence
in tissue of brown-walled, round, nonbudding fungal
elements called sclerotic bodies. Sclerotic bodies are
typically divided by intersecting septa in more than one
plane, longitudinal and transverse, and they represent
the distinctive histopathological feature of human
chromoblastomycosis.1 Chromoblastomycosis has
been described only in humans, most commonly inthe form of verrucous plaques and nodules on feet
and legs.
Aetiologic agents of human chromoblastomycosis
include, Cladophialophora carrionii, Exophiala jeanselmei,
Exophiala spinifera, Fonsecaea pedrosoi, Phialophora
verrucosaand Rhinocladiella aquaspersa.1
Fonsecaea pedrosoi is the most common aetiologic
agent of human chromoblastomycosis in tropical and
subtropical regions of America, and in Asia, Australia
and Europe, mostly the eastern countries.11However,
F. pedrosoi may cause both human chromoblasto-
mycosis and phaeohyphomycosis.
1
Because the same species of fungi can cause different
clinicalpathological entities, and due to the confusing
taxonomy of the commonly implicated organisms in
diseases caused by dematiaceous fungi, in our view, the
change of nomenclature advocated by the Inter-
national Society for Human and Animal Mycology
in 1992 should be applied. According to this change,
the conventional clinical diagnosis should be followed
by the name of the fungus,12 therefore our case
would have been accurately described as a dermal
pyogranuloma caused by Fonsecaea pedrosoi.
The diagnosis of phaeohyphomycosis in our case
was based on the clinicalpathological findings. Adiagnosis of black-grain eumycotic mycetoma was
ruled out based on the absence of two of the clinical
findings typical of mycetoma, which are draining tracts
Figure 5. Slide culture of Fonsecaea pedrosoi. Conidial struc-
tures Rhinocladiella type bearing two rows of conidia, (a) one
playing the role of conidiogenuos cell and (b) one conidial
structure Cladosporium type. Phialides Phialophora type are
shown in (c).
Figure 6. Slide culture of Fonsecaea pedrosoi. Flask-shaped phialide
of Phialophoratype (arrow).
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2001 Blackwell Science Ltd, Veterinary Dermatology, 12, 297301
and granules in the exudate. Typical sclerotic bodies,
which are considered characteristic of human chromo-
blastomycosis, were not observed on the histological
examination of the cutaneous biopsy, therefore our
diagnosis was feline phaeohyphomycosis. The small
clusters of brown globose cells visualized on histo-
pathology were interpreted as transverse sections ofpigmented hyphae or pigmented yeast-like cells. How-
ever, they may represent stages of the development of
sclerotic bodies, typical of chromoblastomycosis, in
which the secondary septa had yet to be formed. His-
topathological pictures depicting such cell clusters
formed by F. pedrosoihave been reported in cases of
human chromoblastomycosis.1Moreover, histopatho-
logical human diagnostic criteria to differentiate
phaeohyphomycosis from chromoblastomycosis
have not yet been recognized unanimously in feline
medicine. In fact, sclerotic bodies have been described
in cases of feline phaeohyphomycosis.10
Because of the route of entry of fungal organisms,
which is from contaminated wounds, feline phaeohy-
phomycosis occurs most commonly as a single nodular
lesion, variably ulcerated, on a distal extremity. Inhala-
tion of airborne fungal elements has been hypothesized
to represent the route of infection in cases of dissemin-
ated disease.9In our case, the presenting signs and the
lack of history of nasal skin wounds would have been
compatible with primary respiratory fungal coloniza-
tion. Sneezing may have been due to nasal mucosal
swelling, undetectable on routine films. However, fungal
colonization in our case should have been limited to
the initial respiratory tract, in fact dissemination of theinfection and underlying immunosuppression were not
detected.
However, penetration of fungal elements by wound
contamination could not be ruled out; in fact, as also
in human phaeohyphomycosis, precipitating trauma at
the site is seldom recalled because lesions are often
present for months or years before coming to medical
attention. The insect sting/ bite might have represented
the source of infection. Human chromoblastomycosis
provoked by an insect bite has been reported13 and
F. pedrosoi has been isolated from abandoned wasp
nests.
14
Furthermore, the black dot observed initiallyby the owner on the skin surface might have repres-
ented dried blood from the wasp sting or from other
trauma. It seems unlikely that the black dot might
have represented pigmented fungal elements elim-
inated transepidermally, as described in human chro-
moblastomycosis,15because the nasal swelling was not
clinically evident at that time.
The treatment choice in our case was based on a pre-
vious report of feline granulomatous rhinitis due to
phaeohyphomycosis which was treated successfully with
itraconazole.16In addition, F. pedrosoi, at least in vitro,
has been reported to be susceptible to itraconazole.17
Complete surgical resection of small lesions, with awide surgical margin of healthy tissue, in feline and
human phaeohyphomycosis and in human chromob-
lastomycosis may be curative. However, total cure is
generally not achieved and recurrence is common.
Medical treatment of nonresectable lesions is difficult
and, to date, a treatment of choice has not been found.
Ketoconazole, itraconazole, amphotericin B and flucy-
tosine have been used alternatively with variable results
to treat feline phaeohyphomycosis.9Amphotericin B,
flucytosine, azoles, triazoles, terbinafine and combineddrug regimens, with or without physical treatment,
have been used alternatively over the years to treat both
human phaeohyphomycosis and chromoblastomyco-
sis with variable results.18In our case, medical treat-
ment with itraconazole was able to induce clinical
remission, but relapses occurred twice. This may be due
to insufficient duration of treatment, which in humans
may last up to 3 or 4 years, although treatment was
maintained for 3 and 5 months, respectively, after signs
of the disease disappeared. However, F. pedrosoiis the
causal agent of chromoblastomycosis least susceptible
to antifungal chemotherapy and this might account
for therapeutic failure.11
The use of newer azoles to treat feline dermal and
subcutaneous fungal infections needs further evalu-
ation. In fact, there are few reported cases regarding the
effectiveness of the triazoles for these diseases in cats.9
In humans they seem to achieve clinical cure, singly
or in combination, but the dose and the duration of
therapy appear to be high and prolonged.11
ACKNOWLEDGEMENTS
The authors would like to thank Prof. Claude DeBivre (Institut Pasteur, Paris) for his supervision in the
identification of Fonsecaea pedrosoiand Prof. Luis Ferrer
for the scientific supervision of the manuscript.
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Rsum Cet article prsente le premier cas de phaeohyphomycose fline d Fonsecaea pedrosoi. Fonsecaea
pedrosoiest responsable chez lhomme de phaeohyphomycose et de chromoblastomycose. Pour notre animal, lalsion tait limite la peau sous la forme dun paississement ferme du chanfrein. Le diagnostic a t ralis
par lexamen histopathologique dune biopsie cutane et par culture fongique sur milieu de Sabouraud. Des tests
supplmentaires nont pas permis de rvler dimmunodficit chez cet animal. Deux cures ditraconazole la dose
de 5 mg kg1deux fois par jour per os ont permis une gurison complte, mais des rcidives sont apparues.
[Fondati, A., Grazia Gallo, M., Romano, E., Fondevila, D. A case of feline phaeohyphomycosis due to Fonsecaea
pedrosoi. (Un cas de phaeohyphomycose due Fonsecaea pedrosoichez un chat.) Veterinary Dermatology12:
297301.]
Resumen Se presenta el primer caso clnico de feohifomicosis felina debida a Fonsecaea pedrosoi. Fonsecaea
pedrosoies un agente etiolgico tanto en la feohifomicosis felina como en la cromoblastomicosis. En nuestro gato,
la lesin se encontraba confinada a la piel y apareca como una tumefaccin dura en el puente nasal. El diagnstico
se bas en el estudio histolgico de biopsias cutneas y en el cultivo fngico de una muestra de biopsia en agar
dextrosa Sabouraud. Otras pruebas llevadas a cabo no mostraron una inmunosupresin subyacente. Dos ciclosde tratamiento con itraconazole, con una dosis de 5 mg kg1administrada dos veces al da, llevaron a una remisin
clnica completa, aunque se produjeron recidivas. [Fondati, A., Grazia Gallo, M., Romano, E., Fondevila, D.
A case of feline phaeohyphomycosis due toFonsecaea pedrosoi. (Un caso de feohifomicosis felina debida a
Fonsecaea pedrosoi.) Veterinary Dermatology12: 297 301.]
Zusammenfassung Der erste Fallbericht von feliner Phohyphomykose verursacht durch Fonsecaea pedrosoi
wird vorgestellt. Fonsecaea pedrosoiist ein tiologisches Agens von humaner Phohyphomykose und Chromob-
lastomykose. Bei dieser Katze war die Lsion auf die Haut beschrnkt und erschien als feste Schwellung auf dem
Nasenrcken. Die Diagnose basierte auf der histologischen Untersuchung einer Hautbiopsie und der Pilzkultur
einer Gewebsprobe auf Sabourauds Dextroseagar. Weitere diagnostische Untersuchungen konnten keine
Immunsuppression nachweisen. Zwei Behandlungszyklen mit Itrakonazol in einer Dosierung von 5 mg kg1
zweimal tglich fhrten zur kompletten klinischen Remission, aber Rezidive traten auf. [Fondati, A., Grazia Gallo, M.,
Romano, E., Fondevila, D. A case of feline phaeohyphomycosis due to Fonsecaea pedrosoi. (Ein Fall von feliner
Phohyphomycose verursacht durch Fonsecaea pedrosoi.) Veterinary Dermatology12: 297 301.]