Hong Kong J. Dermatol. Venereol. (2014) 22, 85-89

Case Report

Cutaneous phaeohyphomycosis in an immunocompromisedhost

YXE Tay , JY Pan , SSJ Lee

Phaeohyphomycosis is an infection caused by dematiaceous fungi in which fungi are present asyeast-like cells or hyphal elements. We report a case of phaeohyphomycosis of the right forearm ina 72 year-old patient with low grade B cell lymphoma and background endogenous eczema. Anunusual feature of this case is that tissue fungal cultures isolated two fungal species, namely Exophialajeanselmei and Cladophialophora species. We seek to highlight phaeohyphomycosis as an emergingmycosis in immunocompromised patients. Physicians should also maintain a high clinical suspicionfor unusual skin signs in immunocompromised individuals as they are more prone to developingopportunistic skin infections.

B

Cladophialophora

Keywords:Keywords:Keywords:Keywords:Keywords: Cladophialophora, dematiaceous fungi, Exophiala jeanselmei, immunocompromised,Phaeohyphomycosis

Cladophialophora

National Skin Centre, SingaporeNational Skin Centre, SingaporeNational Skin Centre, SingaporeNational Skin Centre, SingaporeNational Skin Centre, SingaporeYXE Tay, MBBS, MRCPJY Pan, MRCP, FAMSSSJ Lee, MRCP, FAMS

Correspondence to: Dr. Tay Yuxin Evelyn

National Skin Centre, 1 Mandalay Road, Singapore 308205

IntroductionIntroductionIntroductionIntroductionIntroduction

In recent years, there has been an increasedincidence of phaeohyphomycosis, especially

among a group of immunosuppressed hosts.Coined by Ajello in 1979,1 phaeohyphomycosisrefers to an infection caused by dematiaceousfungi, in which isolated pigmented fungalelements are characterised by the presence ofseptate hyphae, yeasts or yeast-like forms.Phaeohyphomycosis can be further classified intofour categories: i) superficial, ii) cutaneous andcorneal, iii) subcutaneous and iv) systemic.2 Wehighlight a case of cutaneous phaeohyphomycosisin an immunocompromised host, in which twofungal species were isolated.

YXE Tay et al86

Case reportCase reportCase reportCase reportCase report

In June 2010, a 72 year-old Chinese womanpresented with a pruritic plaque over her rightforearm for two months. She did not experienceany fever, chills, rigors or weight loss. There wasno antecedent trauma. Her other medicalproblems included low grade lymphoplasmacyticlymphoma for which she had declined treatment.In the three months prior to presentation, she wasalso receiving up to 40 mg of prednisolone perday for auto-immune haemolytic anaemia. Inaddition, she was on follow-up in our institutionfor mild endogenous eczema.

Examination revealed an erythematous,vesiculated plaque on her right forearm with noregional lymphadenopathy (Figure 1A). She wasinitially treated as eczema herpeticum with oralacyclovir with poor response. A course ofcephalexin was then initiated for empiricaltreatment of infected eczema but the plaque inher forearm increased in size. A biopsy of the skinlesion was then performed.

Histological analysis revealed that there was anulcer to the level of the lower reticular dermis(Figure 1B). There were abundant fungal hyphalelements within the ulcer cavity (Figure 1C).

Figure 1.Figure 1.Figure 1.Figure 1.Figure 1. (A) An erythematous, vesiculated plaque on the flexor surface of the right forearm. (B) Ulcer withgranulomatous inflammation (Haematoxylin-eosin stain; x40). (C) Granulomatous infiltrate with neutrophilsand multinucleated giant cells at the base of ulcer (Haematoxylin-eosin stain; x200). (D) Yeast-like forms inclusters and chains as well as septated hyphae within the giant cells (Periodic Acid-Schiff stain; x400).

Phaeohyphomycosis 87

biopsy , obta ined two months a f ter thep r e v i o u s b i o p s y , r e v e a l e d c o m p a c thyperkera tos i s , pseudoepi the l iomatoushyperplasia, and a dermal infiltrate consistingtuberculoid granulomas, lymphocytes andneutrophils (Figure 2B). Light brown fungalelements exhibiting yeast-like forms in chainsand clusters, as well as septate hyphae wereseen within multinucleated giant cells (Figures2C & 2D). Fungal cultures grew Exophialajeanselmei.

Surrounding the ulcer were neutrophils, epithelioidhistiocytes and multinucleated giant cells (Figure1D). No sclerotic bodies were visualised andZiehl-Neelsen stain did not reveal any acid-fastbacilli. Fungal cultures eventually isolatedCladophialophora species.

She was started on terbinafine but the lesionpersisted and evolved. Crusted vesicles andsuperficial pustules on an erythematous basewere visualised (Figure 2A). A repeat skin

Figure 2.Figure 2.Figure 2.Figure 2.Figure 2. (A) Two months later, there was a crusty erythematous plaque with overlying vesicles and pustules.(B) Compact hyperkeratosis and pseudoepitheliomatous hyperplasia with a dermal infiltrate of lymphocytes,histiocytes and tuberculoid granulomas were visualised (Haematoxylin-eosin stain; x100). (C) Neutrophilsand pigmented yeast-like forms in chains and clusters (bold arrows) within multinucleated giant cells wereseen (Haematoxylin-eosin stain; x400). (D) Yeast-like forms in clusters and chains as well as septatedhyphae within the giant cells (Periodic Acid-Schiff stain; x400).

YXE Tay et al88

Surgical opinion was obtained with regard to thepossibility of excision but poor wound healing wasa concern. A six-month course of itraconazole at200 milligrammes per day was then completedwith complete clinical resolution. Fourteen monthsafter the cessation of itraconazole, the patientremains well with no evidence of recurrence.

DiscussionDiscussionDiscussionDiscussionDiscussion

More than 100 species and 60 genera ofdematiaceous fungi have been associated withcutaneous phaeohyphomycosis.3 Common fungalisolates in subcutaneous phaeohyphomycosisinclude Exophiala jeanselmei, Wangielladermatitidis and Bipolaris species.4 More unusualfungi such as Colletrichium species are beingisolated in immunocompromised hosts.5

Cutaneous phaeohyphomycosis is a growing entityamong immunocompromised populations, withincreasing prevalence among solid-organtransplant recipients who are iatrogenicallyimmunosuppressed.6

The usual presentation is that of an indolent, cysticand solitary nodule that is localised to theextremities. A history of inoculation after traumamay be elicited, or plant fragments identified onbiopsy. In contrast, clinical presentation is morepleomorphic in immunosuppression, with anincreased propensity for multiple nodules withdraining sinuses, pustular plaques, ulcers and eveneschars in disseminated disease.7 Our patient, whohad a haematological malignancy and was onsteroid therapy, also presented atypically.

Other differential diagnoses to be considered inan immunocompromised host include deepfungal infections such as eumycetoma orchromoblastomycosis and atypical mycobacterialinfections. Given the patient's background ofendogenous eczema, we also considered thedifferential diagnoses of eczema herpeticum andsecondary bacterial infection of an eczematousplaque.

Histological analysis may reveal a localisedabscess surrounded by dense collagenousdeposition that gives the appearance of apseudo-cyst. The centre of the abscess is filledwith necrotic debris and fungal elements, withsurrounding palisading macrophages andmultinucleated giant cells. Less commonly,histology may reveal epidermal hyperplasiaand a granulomatous infiltrate in the dermis,8

as in the case of our patient. This pattern issimilar to chromoblastomycosis, which is oftenmistaken for phaeohyphomycosis. Hence, inphaeohyphomycosis, it is important to note thelack of pathognomonic muriform scleroticbodies of chromoblastomycosis on biopsy.2

Despite the identification of dematiaceous fungion histology, definitive cultures should be obtainedto guide treatment and aid prognostication. Somefungi may have an increased propensity fordissemination or have a tropism for certainorgans. For example, Cladosporium bantianumhas a tendency for central nervous system spread.5

A unique feature in this case is the isolation oftwo fungal species on biopsies spaced two monthsapart. To the best of our knowledge, this has onlybeen reported twice in the literature. One was acase of re-infection, in which Alternaria alternatawas first identified from a cyst which recurred 12months later and cultures isolated Colletotrichumgloesporidoides.6 The second was the presentationof seborrhoeic-keratoses like lesions on thescrotum of an immunocompromised host, whichwas diagnosed as co-infection with Bipolarisspecies and Curvularia species.9 The isolation ofExophiala jeanselmei and Cladophialophora sppin our case could indicate that there was a re-infection in a susceptible host. There could alsohave been contamination by either fungi as bothare ubiquitous in the environment. Less possibly,there could have been co-infection with the twospecies in the first place but only one species wasidentified at each time. Colonies of dematiaceousfungi can occasionally produce colonies withbarely perceptible differences. On Sabouraud

Phaeohyphomycosis 89

dextrose agar, Cladophialophora speciesproduces powdery, dark gray to black coloniesand Exophiala jeanselmei produces olive-brownto black velvety colonies.

Surgical excision is generally recommended, butis not always possible, as in the case of ourpatient.5 Itraconazole, which demonstrates aconsistent in vitro antifungal activity against manyspecies of dematiaceous fungi and has a goodsafety profile, has been recommended as the firstline antifungal agent of choice.10 Combinationtherapy with surgical excision and a six-monthcourse of itraconazole has proven to be aneffective regimen in renal transplant patients.6

Owing to the heterogenous presentation ofsubcutaneous phaeohyphomycosis and thevariable level of immunosuppression in patientswith the disease, management should always beindividually tailored.

ConclusionConclusionConclusionConclusionConclusion

We seek to highlight phaeohyphomycoses as anemerging mycosis in immunocompromised hosts.The physician should always look out for anyunusual skin signs in the immunocompromised,as they are more prone to developing opportunisticin fec t ions . Phaeohyphomycos i s in theimmunocompromised individual presents morevariably and, as a result, it may be more difficultto make the diagnosis. The possibility of a co-infection or re-infection with different species of

dematiaceous fungi is also raised in this casereport, and physicians should be aware of thispossibility in a recurrent skin lesion or a lesionunresponsive to appropriate antifungal treatment.

RRRRReferenceseferenceseferenceseferenceseferences

1. Ajello L. The black yeasts as disease agents: historicalperspective. Pan Am Health Organ Sci Pub 1978;356:9-16.

2. McG inn i s MR . Ch romob la s t omycos i s andphaeohyphomycosis: new concepts, diagnosis andmycology. J Am Acad of Dermatol 1983;8:1-16.

3. Rinaldi MG. Phaeohyphomycosis. Dermatol Clin 1996;14:147-53.

4. Pang KR, Wu JJ, Huang DB, Tyring SK. Subcutaneousfungal infections. Dermatol Ther 2004;17:523-31.

5. O’Quinn RP, Hoffmann JH, Boyd AS. Colletotrichumspecies as emerging opportunistic fungal pathogens: Areport of 3 cases of phaeohyphomycosis and review.J Am Acad Dermatol 2001;45:56-61.

6. Ogawa MM, Galante NZ, Godoy P, Fischman-Gompertz O, Martelli F, Colombo AL, et al. Treatmentof subcutaneous phaeohyphomycosis and prospectivefollow-up of 17 kidney transplant recipients. J Am AcadDermatol 2009;61:977-85.

7. Ben-Ami R, Lewis RE, Raad II, Kontoyiannis DP.Phaeohyphomycosis in a tertiary care cancer center. ClinInfect Dis 2009;48:1033-41.

8. Ronan SG, Uzoaru I, Nadimpalli V, Guitart J, ManaligodJR. Primary cutaneous phaeohyphomycosis: report ofseven caases. J Cutan Pathol 1993;223-8.

9. Duvic M. Superficial Phaeohyphomycosis of the Scrotumin a Patient with the Acquired ImmunodeficiencySyndrome. Arch Dermatol 1987;123:1597-8.

10. Garnica M, Nucci M, Queiroz-Telles F. Difficult mycosesof the sk in: advances in epidemiology andmanagement of eumycetoma, phaeohyphomycosisand chromoblastomycosis. Curr Opin Infect Dis 2009;22: 559-63.