Open Access
How to translate text using browser tools
3 May 2023 Multifocal cutaneous phaeohyphomycosis caused by Exophiala spinifera with clinical resolution in an immunocompromised cat
Jevgenija Kondratjeva, Charline Pressanti, Brice S Reynolds, Catherine Trumel, Maxence Delverdier, Anne-Cécile Normand, Nicolas Soetart, Jacques Guillot, Marie Christine Cadiergues
Author Affiliations +

Case summaryA 3-year-old neutered domestic shorthair cat with a long history of idiopathic immune-mediated haemolytic anaemia and thrombocytopenia treated with ciclosporin and prednisolone was referred 2 months after the appearance of nodular dermatitis. A single pigmented nodule was present in the lateral carpal region of the right foreleg. The lesion was 7 mm in diameter, non-exudative and cutaneous to subcutaneous. Fine-needle aspiration of the mass revealed the presence of pigmented fungal elements. Excisional surgery was planned; in the meantime, a plaque-like lesion developed in the interorbital region. Histopathological examination confirmed the presumptive diagnosis of phaeohyphomycosis, and Exophiala spinifera was identified as the aetiological agent. Itraconazole, given orally at a dose of 10 mg/kg for 8 weeks following surgery, enabled clinical resolution despite continued use of immunosuppressants. The follow-up was carried out over 14 weeks.

Relevance and novel informationThis case report provides the first evidence of multifocal cutaneous phaeohyphomycosis caused by E spinifera with clinical resolution after combined surgical and itraconazole treatment in an immunocompromised cat.


Deep mycoses comprise cutaneous and subcutaneous infections, sometimes as manifestations of a systemic disease caused by a diverse group of fungi and pseudofungi.1 Three major aetiological categories of subcutaneous mycoses are recognised: phaeohyphomycosis, hyalohyphomycosis and eumycotic mycetoma.24 Phaeohyphomycosis is caused by dematiaceous fungi that produce melanin-pigmented hyphae and yeast-like forms in tissues and in culture.2,5 Clinically, phaeohyphomycosis often presents as pigmented, ulcerated, crusting or fistulising nodules, non-ulcerated nodules and/or plaques, which can be focal or multifocal and locally invasive. In cats, the areas typically affected are face, distal limbs and tail.2,5

Dematiaceous fungi are rarely pathogenic in immunocompetent hosts, but have recently emerged as important causes of comorbidity in immunocompromised dogs and cats. The apparent increase in their prevalence is possibly due to improved veterinary diagnostic techniques.2,6 Their precise diagnosis, treatment options and data dissemination are important in both human and veterinary medicine.

The development of molecular identification of fungi has facilitated accurate species identification. To date, the genera Exophiala, Fonsecaea, Macrophomina, Microsphaeropsis, Moniliella, Phialophora, Phoma, Scolecobasidium and Stemphylium have been reported to cause diseases in cats.2,3,5 Exophiala species are one of the most frequently recognised agents in human and feline phaeohyphomycoses.79 Exophiala spinifera is one of the most aggressive species of the genus.10 It is associated with severe infections and has an 80% mortality rate in systemic human cases.11 Virulence has been attributed to extracellular polysaccharides produced by yeast-like elements that prevent phagocytes from acting upon tissue invasion.10,12,13 To date, four feline cases caused by E spinifera have been reported in the literature, three in Australia7,14 and one in France,15 all four with a poor outcome.

Herein, we report a positive outcome of multifocal cutaneous phaeohyphomycosis caused by E spinifera in an immunocompromised cat following combined surgical and medical treatment.

Case description

A 3-year-old neutered domestic shorthair cat was referred for a nodular dermatitis that had appeared 2 months previously. The cat lived in southwest France but had spent several months in the Central African Republic when it was 1 year old. The cat had access to the outdoors, and its owner reported regular fights with other cats. About 18 months previously, the cat had been diagnosed with idiopathic immune-mediated haemolytic anaemia and thrombocytopenia (IMHA/IMT) but had been relatively stable for the past 10 months on oral ciclosporin (Atopica chat 100 mg/ml; Elanco) at a dosage of 7.4 mg/kg q24h and oral prednisolone (Prednicortone 20 mg; Dechra) at a dosage of 2.5 mg/kg q48h. The cat had recently developed one nodule on the lateral carpal of the right foreleg. The lesion was 7 mm in diameter, cutaneous to subcutaneous, pigmented, soft, haired, non-painful and non-productive (Figure 1). This lesion was reported to have grown slowly, without disturbing the cat. No other dermatological or clinical abnormalities were observed.

Figure 1

Right forelimb with a nodular lesion, 7 mm in diameter, cutaneous to subcutaneous, pigmented, soft, haired, non-painful and non-productive


The history (immunocompromised cat with access to the outdoors) and clinical features were most consistent with the hypotheses of a cutaneous/subcutaneous infection (pseudomycetoma, leprosy syndrome, other opportunistic mycobacteria, phaeohyphomycosis, hyalohyphomycosis, eumycotic mycetoma, cryptococcosis, sporotrichosis, poxvirus infection, leishmaniosis), neoplasms (melanoma, haemangioma, feline progressive histiocytosis, mastocytoma) and, less likely, sterile granuloma.

Fine-needle aspirates were taken from the nodule, and smears were May–Grünwald–Giemsa stained. Cytological examination revealed damaged inflammatory cells suggestive of neutrophils and the presence of multiple pigmented fungal elements, leading to a diagnosis of phaeohyphomycosis without precise identification of the fungal species involved (Figure 2).

Figure 2

Fine-needle aspire of the nodule. Damaged inflammatory cells suggestive of neutrophils and multiple pigmented fungal elements (arrows point to May–Grünwald–Giemsa staining, magnification × 1000)


Surgical excision was proposed as part of the therapeutic regimen, and also to provide material for histological examination and mycological culture, and was accepted by the owner. On the day of the surgery, 1 month after the initial presentation, the nodule was slightly larger (approximately 1 cm in diameter), and a pigmented plaque-like lesion had appeared between the eyes (Figure 3). Complete excision of the limb nodule and a 4 mm punch biopsy of the plaque were performed under general anaesthesia. Oral itraconazole (Itrafungol; Virbac) at a dosage of 10 mg/kg q24h was started on the same day.

Figure 3

Plaque-like lesion located in the interorbital region


Microscopic appearance was similar for both lesions and was characterised by diffuse, superficial and deep dermal (Figure 4a,b) histiocytic, lymphocytic and, to a lesser extent, neutrophilic infiltrate, with numerous spherical elements, measuring 3–20 µm in diameter, often isolated or with narrow-based buds, surrounded by a basophilic capsule (Figure 4c). Periodic acid–Schiff staining revealed that the elements were positive (Figure 4d). The margins of the nodule appeared to be free of fungal elements.

Figure 4

Histopathological examination of the nodule removed from (a) the right forelimb and (b) the biopsy of the plaque-like interorbital lesion, showing a nodular-to-diffuse superficial and deep dermal dermatitis (haematoxylin and eosin staining, magnification × 40, bars = 1000 µm [a] and 500 µm [b]). (c) The infiltrate was histiocytic, lymphocytic and, to a lesser extent, neutrophilic, with numerous spherical elements, 3–20 µm in diameter, often isolated or with narrow-based buds, pigmented, surrounded by a basophilic capsule (black arrows, haematoxylin and eosin staining, magnification × 400, bar = 10 µm). (d) Periodic acid–Schiff staining showed that the elements were positive (magnification × 400, bar = 10 µm)


The fungus was cultured on Sabouraud dextrose agar plates complemented with 0.5 g/l chloramphenicol for 11 days at 27°C and 37°C and yielded colonies of a black yeast-like fungus (Figure 5). The fungus was identified through macroscopic and microscopic observations, confirmed by mass spectrometry (matrix-assisted laser desorption/ionisation–time of flight mass spectrometry) and molecular biology. Mass spectra were acquired after complete protein extraction using a Microflex LT/HS (Bruker Daltonik) and matched against the online application MSI-2 ( The species E spinifera was identified by mass spectrometry. Confirmation was obtained using Sanger DNA sequencing of internal transcribed spacer regions. The DNA sequence was compared with sequences in the NCBI GenBank database using the Basic Local Alignment Search Tool. The best match (99.8% identity) was with E spinifera, strain CNRMA6.306 (GenBank accession number KP132129.1). The sequences have been deposited in Genbank (accession number OQ466703).

Figure 5

(a) Appearance of the fungal colonies after incubation on Sabouraud dextrose agar for 11 days at 37°C. The colonies were black, slimy at the centre due to yeast-like growth and smooth near the margin. (b) Microscope images (× 400 magnification) of the fungus. Brownish septate hyphae and numerous conidia (some with annellated zones, representing germinating cells) are visible


To investigate the antifungal susceptibility of the isolate, minimal inhibitory concentrations (MICs) were identified using the concentration gradient band (E-test; Biomérieux). The tests showed sensitivity to voriconazole, posaconazole, itraconazole and amphotericin B (MIC 0.023 µg/ml, 0.008 µg/ml, 0.006 µg/ml and 0.19 µg/ml, respectively) and resistance to fluconazole (MIC 24 µg/ml). Based on these results, itraconazole was maintained.

At the 8-week follow-up evaluation, the excisional wound had completely healed and no relapse was visible. Clinical resolution of the non-excised facial lesion was observed. Itraconazole was continued for six more weeks and stopped. Immunosuppressive therapy (ciclosporin and prednisolone) was continued to prevent relapse of IMHA/IMT.


Immunocompromised individuals are much more prone to developing phaeohyphomycosis than immunocompetent individuals. In humans, cases are frequently associated with glucocorticoid therapy,16 whereas in companion animals, one of the predisposing factors is medium–long-term ciclosporin therapy, particularly if combined with other immunosuppressants.2,5,6 This may be related to the main target of ciclosporin, T-helper cells, thus depriving the host of critical defence against fungal infection.2 In the present case, the cat was under immunomodulatory therapy aimed at controlling immune-mediated haemolytic anaemia and thrombocytopenia, with no underlying cause identified, despite extensive work-up. The haematological abnormalities were difficult to control and only partial improvement was obtained by combining ciclosporin and prednisolone, both at a relatively high dosage/frequency over a long period of time. The lifestyle of the cat (access to outdoors, fights with other cats) was also a predisposing factor, increasing the risk of inoculation through traumatic wounds.

The clinical presentation of cutaneous phaeohyphomycosis comprised focal or multifocal pigmented, ulcerated or non-ulcerated nodules and/or plaques, located on the face, the distal limbs and the tail.2,5 When first presented, a single typical focal nodular lesion was detected; a second, plaque-like lesion (also pigmented) developed during the following weeks. It is difficult to judge whether the second lesion spread from the initial lesion or was due to contamination from the same environmental source. Multifocal and systemic spreading of the disease has been regularly reported, particularly in untreated hosts, both humans and animals.2,5,7,8,17,18 Some of these cases were associated with genetic mutations that affect antifungal defence mechanisms (autosomal recessive CARD9 deficiency).19

Cytological examination of fine-needle aspirates is an important diagnostic step in subcutaneous fungal infection and is easy to perform. In the present case, it allowed for rapid diagnosis of phaeohyphomycosis and, subsequently, a straightforward therapeutic decision. Indeed, fungal culture and subsequent appropriate techniques are indispensable to identify the exact species and assess its antifungal susceptibility.1,2,5

In cats, current treatment recommendations for Exophiala infection are based on a very small number of cases and derive from recommendations in humans.5,11 Whenever possible, surgical excision with wide margins should be performed; in the case of multiple lesions or disseminated infection, itraconazole should be prescribed pending results of the susceptibility test.5,7 Based on multiple reports of antifungal resistance in humans, antifungal susceptibility profiling is recommended.9,13 All previous reported feline cases had poor outcomes: one was lost after initial improvement on ketoconazole;14 one relapsed after withdrawal of ketoconazole and 5-fluorocytosine;14 in the third case, surgery followed by oral administration of ketoconazole and fluconazole was unsuccessful;15 in the last case, the cat did not tolerate itraconazole combined with terbinafine, posaconazole was refused and the cat was eventually euthanased.7 In the present case, improvement was very rapid. Clearly, there is a risk of recurrence, as well as of other opportunistic infections as the cat continues to spend time outdoors and because the immunomodulators cannot be stopped. Indeed, better results would be expected if the immunosuppressive treatment could be stopped or reduced.17 As the underlying disease had been difficult to control, even with a combination of immunosuppressant drugs, alleviating the doses was not envisaged. In humans, like in dogs, interactions between ciclosporin and itraconazole, resulting from inhibition of cytochrome P450 (CYP3A), allow the dose of ciclosporin to be reduced when the two molecules are combined.6,2022 Such interaction is not reported in cats; nevertheless, in a previous study, ketoconazole increased the concentration of ciclosporin in the blood about two-fold after ciclosporin was administered,23 suggesting that the same applies to itraconazole.22


This case report provides the first evidence of multifocal cutaneous phaeohyphomycosis caused by E spinifera with clinical resolution after combining surgical and itraconazole treatments in an immunocompromised cat.


We are grateful to Floriane Hubert and Cécile Roux (Laboniris, Nantes, France) for their valuable technical help.

© The Author(s) 2023

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (

Conflict of interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical approval The work described in this manuscript involved the use of non-experimental (owned or unowned) animals. Established internationally recognised high standards (‘best practice’) of veterinary clinical care for the individual patient were always followed and/or this work involved the use of cadavers. Ethical approval from a committee was therefore not specifically required for publication in JFMS Open Reports. Although not required, where ethical approval was still obtained, it is stated in the manuscript.

Informed consent Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers) for all procedure(s) undertaken (prospective or retrospective studies). For any animals or people individually identifiable within this publication, informed consent (verbal or written) for their use in the publication was obtained from the people involved.



Dehghanpir SD. Cytomorphology of deep mycoses in dogs and cats. Vet Clin North Am Small Anim Pract 2023; 53: 155–173. Google Scholar


Dedeaux A , Grooters A , Wakamatsu-Utsuki N , et al. Opportunistic fungal infections in small animals. J Am Anim Hosp Assoc 2018; 54: 327–337. Google Scholar


Miller RI. Nodular granulomatous fungal skin diseases of cats in the United Kingdom: a retrospective review. Vet Dermatol 2010; 21: 130–135. Google Scholar


Walsh TJ , Dixon DM . Spectrum of mycoses. In: Baron S , (ed). Medical microbiology. 4th ed. Galveston, TX: University of Texas Medical Branch, 1996, 919–925. Google Scholar


Lloret A , Hartmann K , Pennisi MG , et al. Rare opportunistic mycoses in cats: phaeohyphomycosis and hyalohyphomycosis: ABCD guidelines on prevention and management. J Feline Med Surg 2013; 15: 628–630. Google Scholar


Archer TM , Boothe DM , Langston VC , et al. Oral cyclosporine treatment in dogs: a review of the literature. J Vet Intern Med 2014; 28: 1–20. DOI: 10.1111/jvim.12265. Google Scholar


Daly JA , Hubka V , Kubatova A , et al. Feline disseminated cutaneous phaeohyphomycosis due to Exophiala spinifera. Med Mycol Case Rep 2020; 27: 32–35. Google Scholar


Harris JE , Sutton DA , Rubin A , et al. Exophiala spinifera as a cause of cutaneous phaeohyphomycosis: case study and review of the literature. Med Mycol 2009; 47: 87–93. Google Scholar


Liu H , Zhang J , Chen Y , et al. Phaeohyphomycosis due to Exophiala spinifera greatly improved by ALA-PDT: a case report. Photodiagnosis Photodyn Ther 2019; 28: 297–299. Google Scholar


Song Y , da Silva NM , Weiss VA , et al. Comparative genomic analysis of capsule-producing black yeasts Exophiala dermatitidis and Exophiala spinifera, potential agents of disseminated mycoses. Front Microbiol 2020; 11: 586. Google Scholar


Bohelay G , Robert S , Bouges-Michel C , et al. Subcutaneous phaeohyphomycosis caused by Exophiala spinifera in a European patient with lymphoma: a rare occurrence case report and literature review. Mycoses 2016; 59: 691–696. Google Scholar


Song Y , Laureijssen-van de Sande WWJ , Moreno LF , et al. Comparative ecology of capsular Exophiala species causing disseminated infection in humans. Front Microbiol 2017; 8: 2514. Google Scholar


Vitale RG , de Hoog GS. Molecular diversity, new species and antifungal susceptibilities in the Exophiala spinifera clade. Med Mycol 2002; 40: 545–556. Google Scholar


Kettlewell P , McGinnis MR , Wilkinson GT. Phaeohyphomycosis caused by Exophiala spinifera in two cats. J Med Vet Mycol 1989; 27: 257–264. Google Scholar


Chermette R , Ferreiro L , Bièvre Cd , et al. Exophiala spinifera nasal infection in a cat and a literature review of feline phaeohyphomycoses. J Mycol Med 1997; 7: 149–158. Google Scholar


Revankar SG , Baddley JW , Chen SC , et al. A mycoses study group international prospective study of phaeohyphomycosis: an analysis of 99 proven/probable cases. Open Forum Infect Dis 2017; 4. DOI: 10.1093/ofid/ofx200. Google Scholar


Borras P , Messina F , Abrantes R , et al. First report of phaeohyphomycosis caused by Phialophora americana in a domestic cat from Argentina. JFMS Open Rep 2022; 8: DOI: 10.1177/20551169221077611. Google Scholar


Wang L , Wang C , Shen Y , et al. Phaeohyphomycosis caused by Exophiala spinifera: an increasing disease in young females in mainland China? Two case reports and review of five cases reported from mainland China. Mycoses 2015; 58: 193–196. Google Scholar


Lanternier F , Barbati E , Meinzer U , et al. Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala infection. J Infect Dis 2015; 211: 1241–1250. Google Scholar


Florea NR , Capitano B , Nightingale CH , et al. Beneficial pharmacokinetic interaction between cyclosporine and itraconazole in renal transplant recipients. Transplant Proc 2003; 35: 2873–2877. Google Scholar


Matsuda Y , Nakagawa S , Yano I , et al. Effect of itraconazole and its metabolite hydroxyitraconazole on the blood concentrations of cyclosporine and tacrolimus in lung transplant recipients. Biol Pharm Bull 2022; 45: 397–402. Google Scholar


Sasaki K , Shimoda M. Possible drug-drug interaction in dogs and cats resulted from alteration in drug metabolism: a mini review. J Adv Res 2015; 6: 383–392. Google Scholar


McAnulty JF , Lensmeyer GL. The effects of ketoconazole on the pharmacokinetics of cyclosporine A in cats. Vet Surg 1999; 28: 448–455. Google Scholar
Jevgenija Kondratjeva, Charline Pressanti, Brice S Reynolds, Catherine Trumel, Maxence Delverdier, Anne-Cécile Normand, Nicolas Soetart, Jacques Guillot, and Marie Christine Cadiergues "Multifocal cutaneous phaeohyphomycosis caused by Exophiala spinifera with clinical resolution in an immunocompromised cat," Journal of Feline Medicine and Surgery Open Reports 9(1), (3 May 2023).
Accepted: 2 March 2023; Published: 3 May 2023
Exophiala spinifera
Back to Top