Phaeohyphomycosis and hyalohyphomycosis: rare opportunistic mycoses

Edited October 31, 2015

 

The rare opportunistic mycoses guidelines were first published in the J Feline Med Surg 2013; 15: 628-630; the present version has been authorised by Albert Lloret. The ABCD is grateful to Prof. Lluís Ferrer of the Foster Hospital for Small Animals, Cummings School of Veterinary Medicine, Tufts University, USA, who has graciously contributed to this article.

 

 

Fig. 1. Dark-coloured fungal structure in tissue. Courtesy of Prof. Lluís Ferrer, Tufts University, USA

Fig. 1. Dark-coloured fungal structure in tissue. Courtesy of Prof. Lluís Ferrer, Tufts University, USA

 

Fungal properties and epidemiology

 

Phaeohyphomycoses are rare opportunistic fungal infections caused by numerous genera of fungal moulds that characteristically produce melanin-pigmented ”dematiaceous (dark-coloured) hyphal elements in tissues an in culture (Figs. 1, 2), although yeast-like forms have also been found in some cases.1 Hyalohyphomycoses are caused by several genera of fungi, which are non-pigmented, being transparent or hyaline, in tissues.1

 

Fig. 2. "Dematiaceous"(dark-coloured) colony

Fig. 2. “Dematiaceous” (dark-coloured) colony. Courtesy of Prof. Lluís Ferrer, Tufts University, USA

 

Both are ubiquitous saprophytic agents. The number of reports of infections is increasing in humans and animals, often associated with immunosuppressive treatment or an immunosuppressive condition. In human medicine, they are currently considered emerging fungal infections.2,3

 

Infections are acquired from traumatic implantation from the environment (soil and decomposed plants). Direct transmission between hosts does not occur.1

 

The taxonomy of the etiologic agents is complex, and names have often been changed. More than 100 species classified with 60 genera have been described as agents of phaeohyphomycosis in animals and humans. Pathogens for dogs and cats include species from Alternaria, Bipolaris, Cladophialophora and Curvularia. Genera with species causing disease only in cats are Exophiala, Fonsecaea, Macrophomina, Microsphaerosis, Moniliella, Phialophora, Phoma, Scolebobasidium and Stemphyllium.

 

Genera with species causing hyalohyphomycosis in dogs and cats include Fusarium, Acremonium, Paecilomyces, Pseudallescheria, Sagemonella, Phialosimplex, Scedosporium.

 

Feline phaeohyphomycosis probably has a worldwide distribution as sporadic cases have been reported from North America, Spain4, Italy5,6, Australia7, Canada8, the UK9,10 and Japan11.

 

A recent retrospective study from the UK evaluated 77 cats with nodular granulomatous skin lesions caused by fungal infection. The most frequent cause was hyalohyphomycosis. Phaeohyphomycosis and deep pseudomycetomas were less frequently diagnosed.9

 

 

Pathogenesis

 

Infection occurs mainly through contact or skin puncture, especially through trauma involving wood.1 Respiratory tract colonization is suspected to occur in systemic cases. In the rare cases of CNS infection, the route of exposure has not been elucidated, but an extension from sinuses, the orbit and middle ear has been suggested.1,12 Local infections are rarely associated with systemic diseases or immunosuppression.1 The infrequent cases of systemic disseminated infection may or may not be associated with immunosuppression.

 

 

Clinical presentation

 

Nodules or masses in the skin or nasal mucosa are the most common clinical problem. Ulcerated, crusting or fistulating nodules, non-ulcerated subcutaneous nodules and/or plaques, which can be focal or multifocal and locally invasive are typical lesions.4-11 The lesions may appear pigmented,1 but are otherwise not different from chronic bacterial infection or cystic skin lesions. In most cases they are found in the facial region, the distal part of extremities or the tail. A quite typical presentation is a nodule on the bridge of the nose.4 A case of a focal pulmonary granuloma caused by Cladophialophora bantiana has been reported in a cat.13

 

Few cases are in the literature where fungal infections were responsible for multifocal neurological signs due to encephalitis or brain abscesses12 or for disseminated disease14,15, especially in association with immunosuppression. In these cases the causative organism has been identified as Cladosporium spp. Most cases have been diagnosed post mortem.

 

Fig. 3 Pigmented fungal structures in tissue. Courtesy of Prof. Lluís Ferrer, Tufts University, USA

Fig. 3 Pigmented fungal structures in tissue. Courtesy of Prof. Lluís Ferrer, Tufts University, USA

 

Diagnosis

 

Diagnosis is based on visualization of the fungal organism in cytology and/or histology, which usually shows a nodular to diffuse pyogranulomatous inflammation pattern. In tissue, the presence of pigmented fungal structures in the centre of the pyogranulomatous reaction is highly suggestive of phaeohyphomycosis (Fig. 3).1,4-11 Special fungal stains such as the Gömöri methenamine silver or periodic acid-Schiff procedure can enhance the diagnostic sensitivity.

 

Definitive diagnosis is based on fungal culture and identification of the fungal species by morphology and pigmentation features by specialized laboratories.1

 

Molecular techniques have scarcely been used to identify pathogenic fungal species.11

 

 

Treatment

 

No prospective studies exist on the treatment of feline phaeohyphomycosis or hyalohyphomycosis. Recommendations are based on case reports.

 

The treatment of choice is aggressive surgical excision of local lesions, as these rarely respond to antifungal treatment. After surgery of a single lesion, if multiple lesions exist or in cases of disseminated infection, itraconazole is the treatment of choice. Disseminated or neurologic cases are poorly responsive to treatment. Ketoconazole, amphotericin B and posiconazole have been used in few cases.1,13  Table 1 lists the treatment options for these infections.

 

There are no vaccines available.

 

Drug/treatmentDose and frequencyComments
Surgical excisionRadical surgery with wide margins
Itraconazole10 mg/kg PO q24hConsider if multiple lesions or post-surgery
Posaconazole5 mg/kg PO q24hConsider in severe or disseminated disease
Amphotericin B0.25 mg/kg q48h IVConsider in severe or disseminated disease
Table 1. Treatment of phaeohyphomycosis and hyalohyphomycosis

 

Zoonotic risk

 

These fungal agents are acquired from the environment and are not transmitted amongst cats nor to humans.1

 

 

References

 

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

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

3 Fothergill AW. Identification of dematiaceous fungi and their role in human disease. Clin Infect Dis 1996 22(Suppl 2):S179-S184.

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

5 Beccati M, Vercelli A, Peano A, Gallo MG. Phaeohyphomycosis by Phialophora verrucosa: first European case in a cat. Vet Rec 2005; 157:93-4.

6 Abramo F, Bastelli F, Nardoni S, Mancianti F. Feline cutaneous phaeohyphomycosis due to Cladophyalophora bantiana. J Feline Med Surg 2002; 4:157-63.

7 Kettlewell P, McGinnis MR, Wilkinson GT. Phaeohyphomycosis caused by Exophiala spinifera in two cats. J Med Vet Mycol 1989; 27:257-64.

8 Outerbridge CA, Myers SL, Summerbell RC. Phaeohyphomycosis in a cat. Can Vet J 1995; 36: 629-30.

9 Miller RI. Nodular granulomatous fungal skin disease of cats in the United Kingdom: a retrospective review. Vet Dermatol 2010; 21:130-135.

10 Knights CB, Lee K, Rycroft AN, Patterson-Kane JC, Baines SJ. Phaeohyphomycosis caused by Ulocladium species in a cat. Vet Rec 2008; 162: 415-6.

11 Maeda H, Shibuya H, Yamaguchi Y, Miyoshi T, Irie M, Sato T. Feline digital phaeohyphomycosis due to Exophiala jeanselmei. J Vet Med Sci 2008; 70:1395-7.

12 Bouljihad M, Lindeman CJ, Hayden DW. Pyogranulomatous meningoencephalitis associated with dematiaceous fungal (Cladophialophora bantiana) infection in a domestic cat. J Vet Diagn Invest 2002; 14:70-2.

13 Evans N, Gunew M, Marshall R, Martin P, Barrs V. Focal pulmonary granuloma caused by Cladophialophora bantiana in a domestic shorthair cat. Med Mycol 2011; 49: 194-7.

14 Elies L, Balandraud V, Boulouha L, Crespeau F, Guillot J. Fatal systemic phaeohyphomycosis in a cat due to Cladophialophora bantiana. J Vet Med A Physiol Pathol Clin Med 2003; 50:50-3.

15 Mariani CL, Platt SR, Scase TJ, Howerth EW, Chrisman CL, Clemmons RM. Cerebral phaeohyphomycosis caused by Cladosporium spp. in two domestic shorthair cats. J Am Anim Hosp Assoc 2002; 38:225-30.

 

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