a case of feline phaeohyphomycosis due to fonsecaea pedrosoi (pages 297–301)

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  • 8/10/2019 A Case of Feline Phaeohyphomycosis Due to Fonsecaea Pedrosoi (Pages 297301)

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    2001 Blackwell Science Ltd 297

    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:

    [email protected]

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    298 A. Fondati et al.

    2001 Blackwell Science Ltd, Veterinary Dermatology, 12, 297301

    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.

    REFERENCES

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    of Medically Important Fungi and Aerobic Actinomycetes.

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    7. Roosje, P.J., de Hoog, G.S., Willemse, T. Phaeohyphomy-

    cosis in a cat caused by Alternaria infectoriaE. G. Simmons.Mycoses1993; 36: 4514.

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    9. Foil, C.S. Miscellaneous fungal infections. In: Greene, C.E.,

    ed. Infectious Diseases of the Dog and Cat. Philadelphia:

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    10. Scott, D.W., Miller, W.H., Griffin, C.E. Muller and Kirks

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    lastomycosis in India. International Journal of Dermatology1999; 38: 84651.

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    Veterinary Mycology1992; 30: 110.

    13. Sauerteig, E., Hernndez, R., Salfelder, K. et al.Acute

    chromoblastomycosis provoked by an insect bite in an

    immunosuppressed patient. Mycoses1998; 41: 1914.

    14. Kwon-Chung, K.J., Bennet, J.E. Medical Mycology.

    Philadelphia: Lea & Febiger, 1992: 62177.

    15. Wortman, P.D. Concurrent chromoblastomycosis caused

    by Fonsecaea pedrosoi and actinomycetoma caused by

    Nocardia brasiliensis. Journal of the American Academy

    of Dermatology1995; 32: 3902.

    16. Michaud, A.J. Phaeohyphomycosis rhinitis due to

    Exophiala jeanselmeiin a domestic cat. Feline Practice1993; 21: 1923.

    17. de Bedout, C., Gomez, B.L., Restrepo, A. In vitrosuscept-

    ibility testing of Fonsecaea pedrosoi to antifungals.

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    18. Esterre, P., Inzan, C.K., Ramarcel, E.R. et al.Treatment

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    1996; 134(Suppl. 46): 33 6.

    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.]