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http://jfm.sagepub.com/content/15/7/628The online version of this article can be found at:

 DOI: 10.1177/1098612X13489227

2013 15: 628Journal of Feline Medicine and SurgeryD Radford, Etienne Thiry, Uwe Truyen and Marian C Horzinek

Herman Egberink, Tadeusz Frymus, Tim Gruffydd-Jones, Margaret J Hosie, Hans Lutz, Fulvio Marsilio, Karin Möstl, Alan Albert Lloret, Katrin Hartmann, Maria Grazia Pennisi, Lluis Ferrer, Diane Addie, Sándor Belák, Corine Boucraut-Baralon,

on prevention and managementRare opportunistic mycoses in cats: phaeohyphomycosis and hyalohyphomycosis: ABCD guidelines

  

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Fungal properties and epidemiology

Phaeohyphomycoses are rare opportunistic fungal infections causedby numerous genera of fungal moulds that characteristically producemelanin-pigmented ‘dematiaceous’ (dark-coloured) hyphal elementsin tissues and in culture (Figures 1 and 2); yeast-like forms have alsobeen found in some cases.1 Hyalohyphomycoses are caused by severalgenera of fungi that are non-pigmented, being transparent or hyalinein tissues.1Both are ubiquitous saprophytic agents. The number of reports ofinfections is increasingin humans and animals,often associated withimmunosuppressivetreatment or animmunosuppressivecondition. In humanmedicine, they arecurrently consideredemerging fungalinfections.2,3Infections areacquired from trau-matic implantation from the environment (soil and decomposedplants). Direct transmission between hosts does not occur.1The taxonomy of the aetiological agents is complicated, and nameshave often been changed. More than 100 species classified within 60 genera have been described as agents of phaeohyphomycosis in animals and humans. Pathogens for dogs and cats include species fromAlternaria, Bipolaris, Cladophialophora and Curvularia. Genera withspecies causing disease in cats, but not in dogs, are Exophiala, Fonsecaea, Macrophomina, Microsphaerosis, Moniliella, Phialophora, Phoma,Scolecobasidium and Stemphylium.

Journal of Feline Medicine and Surgery (2013) 15, 628–630

C L I N I C A L R E V I E W

RARE OPPORTUNISTIC MYCOSES IN CATS:PHAEOHYPHOMYCOSIS ANDHYALOHYPHOMYCOSISABCD guidelines on prevention and management

Albert Lloret, Katrin Hartmann, Maria Grazia Pennisi, Lluis Ferrer*, Diane Addie,Sándor Belák, Corine Boucraut-Baralon, Herman Egberink, Tadeusz Frymus, Tim Gruffydd-Jones, Margaret J Hosie, Hans Lutz, Fulvio Marsilio, Karin Möstl,Alan D Radford, Etienne Thiry, Uwe Truyen and Marian C Horzinek

628 JFMS CLINICAL PRACTICE

European Advisory Board on Cat Diseases

www.abcd-vets.orgCorresponding author: Albert LloretEmail: Albert.LLoret@uab.cat

European Advisory Board on Cat DiseasesThe European Advisory Board on Cat Diseases (ABCD) isa body of experts in immunology, vaccinology and clinicalfeline medicine that issues guidelines on prevention andmanagement of feline infectious diseases in Europe, for the benefit of the health and welfare of cats. Theguidelines are based on current scientific knowledge ofthe diseases and available vaccines concerned.

The latest version of the rare opportunistic mycosesin cats guidelines is available at www.abcd-vets.org

DOI: 10.1177/1098612X13489227© Published by SAGE on behalf of ISFM and AAFP 2013

Overview: Phaeohyphomycoses andhyalohyphomycoses are rare opportunisticinfections acquired from the environment. More cases have been reported in recent yearsin humans and cats. Disease signs: Single or multiple nodules orulcerated plaques (which may be pigmented) inthe skin are the typical lesions. In some casesthe infection disseminates or involves the centralnervous system (CNS). Diagnosis: Diagnosis is based on fungaldetection by cytology and/or histology. Culture provides definitive diagnosis and species identification. Treatment: Treatment involves surgical excisionin cases of localised skin disease followed bysystemic antifungal therapy, with itraconazole as the agent of first choice. Relapses aftertreatment are common. Itraconazole and othersystemic antifungal agents have been used totreat systemic or neurological cases, but theresponse is unpredictable. The prognosis isguarded to poor in cats with multiple lesions and systemic or neurological involvement. Zoonotic risk: There is no zoonotic riskassociated with contact with infected cats.

*The ABCD is grateful to Professor Lluís Ferrer, of the FosterHospital for Small Animals, Cummings School of VeterinaryMedicine, Tufts University, USA, who, though not a memberof the Board, contributed to this article.

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JFMS CLINICAL PRACTICE 629

Genera with species causinghyalohyphomycosis in dogs and cats include Fusarium,Acremonium, Paecilomyces,Pseudallescheria, Sagemonella,Phialosimplex and Scedosporium.Feline phaeohyphomycosis

probably has a worldwide dis -tribution as sporadic cases have been reported from NorthAmerica, Spain,4 Italy,5,6Australia,7 Canada,8 the UK9,10

and Japan.11A retrospective study from the

UK evaluating 77 cats with nodular granulo-matous skin lesions caused by fungal infectionfound that the most frequent cause washyalohypho mycosis. Phaeohyphomycosis anddeep pseudomycetomas were less frequentlydiagnosed.9

Pathogenesis

Infection occurs mainly through contact orskin puncture, especially through traumainvolving wood.1 Respiratory tract colonisa-tion is suspected to occur in systemic cases. Inthe rare cases of CNS infection, the route ofexposure has not been elucidated, but anextension from sinuses, the orbit and middleear has been suggested.1,12 Local infections arerarely associated with systemic diseases orimmunosuppression.1 The infrequent cases ofsystemic disseminated infection may or maynot be associated with immunosuppression.

Clinical presentation

Nodules or masses in the skin or nasal mucosaare the most common clinical problem.Ulcerated, crusting or fistulating nodules, non-ulcerated subcutaneous nodules and/orplaques, which can be focal or multifocal andlocally invasive, are typical lesions.4–11 Thelesions may appear pigmented,1 but are other-wise not different from chronic bacterial infec-tion or cystic skin lesions. In most cases they

REV IEW / ABCD guidelines on rare opportunistic mycoses

are found in the facial region, and on the distal part of the extremities or the tail. A typ-ical presentation is a nodule on the bridge ofthe nose.4 A case of a focal pulmonary granu-loma caused by Cladophialophora bantiana hasbeen reported in a cat.13A few cases in the literature concern fungal

infections that were responsible for multifocalneurological signs due to encephalitis or brainabscesses12 or for disseminated disease,14,15especially in association with immunosup-pression. In these cases the causative organismhas been identified as Cladosporium species.Most cases have been diagnosed post mortem.

Diagnosis

Diagnosis is based on visualisation of the fungal organism on cytology and/or histol-ogy, which usually shows a nodular to diffusepyogranulomatous inflammation pattern. Intissue, the presence of pigmented fungalstructures in the centre of the pyogranuloma-tous reaction is highly suggestive of phaeo -hyphomycosis (Figure 3).1,4–11 Special fungalstains such as Gomori methenamine silver orperiodic acid-Schiff can enhance the diagnos-tic sensitivity. Definitive diagnosis relies on fungal culture

and identification of the fungal species basedon morphology and pigmentation features byspecialised laboratories.1Molecular techniques have only seldom been

used to identify pathogenic fungal species.11

Treatment

No prospective studies exist on the treatmentof feline phaeohyphomycosis or hyalohypho -mycosis. Recommendations are based on casereports.The approach for local lesions is aggressive

surgical excision, as these rarely respond toantifungal treatment. After surgery of a singlelesion, if multiple lesions exist or in cases ofdisseminated infection, itraconazole is thetreatment of choice [EBM grade IV].

In humanmedicine,these arecurrentlyconsideredemergingfungal

infections.

Figure 1 Dark-coloured, periodic acid-Schiff-positive, fungalstructures in a tissue sample. Courtesy of Alessandra Fondati

Figure 2 ‘Dematiaceous’(dark-coloured) colony.Courtesy of Alessandra Fondati

Figure 3 Pigmented fungal structures in a tissue sample.Courtesy of Lluís Ferrer

EBM gradesThe ranking systemfor grading the levelof evidence ofvarious statementswithin this article isdescribed on page 533 of thisSpecial Issue.

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630 JFMS CLINICAL PRACTICE

REV IEW / ABCD guidelines on rare opportunistic mycoses

Disseminated or neurological cases arepoorly responsive to treatment.Ketoconazole, amphotericin B andposaconazole have been used in a fewcases [EBM grade IV].1,13Table 1 lists the treatment options forthese infections.

< Sporadic cases of these fungal diseases have been reported in cats.

< Skin nodules and ulcers, especially involving the facial area,distal extremities and tail, are the most frequent lesions.

< Dissemination and CNS signs may occur in rare cases, especiallywith Cladosporium species infection.

< Histology and culture are the most useful diagnostic tests. Somefungi show a typical pigmentation, which is helpful for diagnosis.

< A combination of surgery and systemic antifungal treatment(itraconazole) may cure cases with localised lesions.

< Cases of disseminated skin disease or systemic disease have a poor prognosis; new azole drugs like posaconazole should be considered in these cats.

KEY POINTS

Funding

The authors received no specific grant from anyfunding agency in the public, commercial or not-for-profit sectors for the preparation of this article. TheABCD is supported by Merial, but is a scientificallyindependent body.

Conflict of interest

The authors do not have any potential conflicts ofinterest to declare.

References

1 Grooters AM and Foil CS. Miscellaneous fun-gal infections. In: Greene CE (ed). Infectiousdiseases of the dog and the cat. 3rd ed. St Louis:Saunders Elsevier, 2006, pp 637–650.

2 Revankar SG, Patterson JE, Sutton DA, Pullen Rand Rinaldi MG. Disseminated phaeohy-phomycosis: review of an emerging mycosis.Clin Infect Dis 2002; 34: 467–476.

3 Fothergill AW. Identification of dematiaceousfungi and their role in human disease. ClinInfect Dis 1996; 22: S179–S184.

4 Fondati A, Gallo MG, Romano E and Fondevila D.A case of feline phaeohyphomycosis due toFonsecaea pedrosoi.Vet Dermatol 2001; 2: 297–301.

5 Beccati M, Vercelli A, Peano A and Gallo MG.Phaeohyphomycosis by Phialophora verru-cosa: first European case in a cat. Vet Rec 2005;157: 93–94.

6 Abramo F, Bastelli F, Nardoni S and ManciantiF. Feline cutaneous phaeohyphomycosis dueto Cladophyalophora bantiana. J Feline MedSurg 2002; 4: 157–163.

7 Kettlewell P, McGinnis MR and Wilkinson GT.Phaeohyphomycosis caused by Exophialaspinifera in two cats. J Med Vet Mycol 1989; 27:257–264.

8 Outerbridge CA, Myers SL and SummerbellRC. Phaeohyphomycosis in a cat. Can Vet J1995; 36: 629–630.

9 Miller RI. Nodular granulomatous fungal skindisease of cats in the United Kingdom: a retro-spective review. Vet Dermatol 2010; 21: 130–135.

10 Knights CB, Lee K, Rycroft AN, Patterson-KaneJC and Baines SJ. Phaeohyphomycosis causedby Ulocladium species in a cat. Vet Rec 2008;162: 415–416.

11 Maeda H, Shibuya H, Yamaguchi Y, Miyoshi T,Irie M and Sato T. Feline digital phaeohypho -mycosis due to Exophiala jeanselmei. J Vet MedSci 2008; 70: 1395–1397.

12 Bouljihad M, Lindeman CJ and Hayden DW.Pyogranulomatous meningoencephalitis associated with dematiaceous fungal(Cladophialophora bantiana) infection in adomestic cat. J Vet Diagn Invest 2002; 14: 70–72.

13 Evans N, Gunew M, Marshall R, Martin P andBarrs V. Focal pulmonary granuloma causedby Cladophialophora bantiana in a domesticshorthair cat.Med Mycol 2011; 49: 194–197.

14 Elies L, Balandraud V, Boulouha L, Crespeau Fand Guillot J. Fatal systemic phaeohyphomyco-sis in a cat due to Cladophialophora bantiana. JVet Med A Physiol Pathol Clin Med 2003; 50: 50–53.

15 Mariani CL, Platt SR, Scase TJ, Howerth EW,Chrisman CL and Clemmons RM. Cerebralphaeohyphomycosis caused by Cladosporiumspp. in two domestic shorthair cats. J Am AnimHosp Assoc 2002; 38: 225–230.

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Zoonotic riskThese fungal agents are

acquired from the environmentand are not transmitted amongcats or to humans.1

Drug/treatment Dose and frequency Comments

Surgical excision Radical surgery with wide margins

Itraconazole 10 mg/kg PO q24h Consider if multiple lesions or post-surgery

Posaconazole 5 mg/kg q24h PO Consider in severe or disseminated disease

Amphotericin B 0.25 mg/kg q48h IV to a total Consider in severe or disseminated disease

Treatment of phaeohyphomycosis and hyalohyphomycosisTable 1

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