ARTICLE
Auteur(s) : M Covadonga
Martínez-González1, M Magdalena Verea1,
David Velasco2, Felipe Sacristán3, Jesús Del
Pozo1, Jesús García-Silva1, Eduardo
Fonseca1
1Dermatology Service, Abente and Lago Hospital,
Universitary Hospital Complex Juan Canalejo, C/ Sir John Moore,
s/n. 15001- La Coruña. Spain
2Department of Microbiology, Hospital Juan Canalejo, La
Coruña, Spain
3Department of Pathology, Hospital Juan Canalejo, La
Coruña, Spain
accepté le 3 Decembre 2007
Phaeohyphomycosis, a term introduced by Allejo in 1974 [1], is
an opportunistic fungal infection that has been reported in
patients living throughout the world. It includes a heterogeneous
group of mycotic infections that involves dematiaceous yeast-like
cells, pseudohyphae-like elements, hyphae, or any combination of
these in tissues. These organisms are characterized by yellow to
brown pigmentation of their cell walls and distinctive brown to
black colony morphology in fungal cultures [2-4]. They have been
isolated from wood, soil and plant materials, in different
environments and are distributed worldwide as saprophytes [2].
About 104 species of dematiaceous fungi can cause cutaneous
phaeohyphomycosis, but the most frequent etiologic agent is
Exophiala jeanselmei [5]. The affected patients are usually adults
with debilitating diseases [6-8] or immunosuppressive therapies
such as organ transplant recipients [9-11] and systemic steroid
therapies [6, 7], but there are several reports in healthy patients
[7].
A small nodule in an anatomical region more prone to trauma,
which evolves to a cutaneous and subcutaneous cyst or abscess,
showing a chronic course as a slowly progressive disease, is the
most common clinical presentation of phaeohyphomycosis [3].
We describe three cases of localized cutaneous phaeohyphomycosis
in two patients immunocompromised because of systemic steroid
therapy, and one in an elderly woman.
Case reports
Case 1
A 79-year-old white man presented in May 2001 with several
erythematous crusted plaques of 1-2 cm, with a lineal
distribution on his right foot and several tiny pustules, present
since 3 months (figure
1). Oedema was important and the lesions drained purulent
exudate by pressure. He had been treated with topical fusidic acid
and oral amoxycilin-clavulanic acid by his general practitioner
without good results.
His medical history revealed pulmonary emphysema and chronic
obstructive pulmonary disease present for 18 years, duodenal ulcer,
prostate adenoma, auricular fibrillation, and lip squamous cell
carcinoma. His treatments at presentation included: domiciliary
oxygen, prednisone (30 mg/day), digoxin, furosemide,
omeprazole, fluticasone propionate and ipratropio bromide.
The histopathological study of a skin biopsy showed an
inflammatory infiltrate in the papillary dermis forming abscesses
constituted predominantly by neutrophils and surrounded by
multinuclear hystiocytes. Corneal cysts in the follicular
infundibulum were also present. Fungal structures were identified
both among the polymorphonuclear cells and within keratin of the
corneal cysts.
The direct fresh microscopic exam for fungi (10-20% potassium
hydroxide preparations) was negative. Culture of purulent exudate
and biopsy material on Sabouraud’s dextrose agar yielded numerous
fungal colonies of Exophiala jeanselmei.
The patient was treated with 200 mg daily of oral
itraconazole for six months with total clinical response.
Case 2
An 81-year-old white woman presented in April 2005 with an
asymptomatic cutaneous lesion on her left forearm, of two years
evolution. The lesion had been drained approximately one year ago,
but rapidly recurred. Physical skin examination revealed a
poorly-delimited plaque formed by multiple, tiny, grouped,
erythematous, cystic-like, pus-filled lesions on the left forearm
(figure 2). One
larger cyst was punctured, draining purulent exudate. No regional
adenopathies were detected. Her medical history revealed multiple
hospitalizations for cardiac insufficiency, Billroth II
gastrectomy, hysterectomy, endoscopic polypectomy and colonic
diverticulum with secondary rectal haemorrhage. Her treatments at
presentation included: furosemide, digoxin, ferrum, diazepam,
acenocoumarol, omeprazole and fluvoxamine. Haematological studies
revealed only a moderate microcytic and hypochromic anemia.
Microscopic study of the biopsy showed a supurative dermal
inflammatory reaction with granulomas affecting the dermis and
subcutis. Some granulomas had a central cystic space containing
neutrophils (figure
3). Mixed with this inflammatory reaction were pigmented
yeast-like structures and pigmented hyphae, positive with
Masson-Fontana (figure
4) and periodic acid-Schiff (PAS) stains. Using polarizing
plates, no birefringent material was found within the granulomas.
The Ziehl-Neelsen stain showed no acid fast resistant bacilli.
The direct fresh microscopic exam for fungi (10-20% potassium
hydroxide preparations) was negative. Nevertheless, culture of pus
on Sabouraud’s dextrose agar medium yielded numerous fungal
colonies of Exophiala jeanselmei. Minimal inhibitory concentration
(MIC) to itraconazole was 0.008 μg/mL.
Oral itraconazole (100 mg/day) was started for three
months, but the patient failed to follow the treatment and the
cystic lesions enlarged. We drained the abscess and replaced the
treatment by terbinafine 100 mg daily during three months with
total clinical response.
Case 3
A 59-year-old white woman presented with asymptomatic, gradually
enlarging, cutaneous lesions on both arms and the left buttock, of
4 months duration. Physical skin examination revealed three
abscesiform cutaneous lesions, poorly-delimited, with off-white
content, of about 2 cm diameter, on both arms and the left
buttock. Her medical history revealed hypothyroidism, vulvar
squamous cell carcinoma treated only with surgical exeresis,
polymyositis diagnosed in 1994, with interstitial pulmonary
affectation, severe secondary pulmonary hypertension and secondary
respiratory insufficiency. In the past she had received
immunosuppressive treatment with azathioprine and cyclophosphamide
and, on presentation, she was receiving prednisone
(20 mg/day). She also had domiciliary oxygen, acenocoumarol,
omeprazole, furosemide, diazepam, levothyroxine, folic acid, calcic
carbonate and colecalciferol.
Haematological studies revealed moderate increased findings in
sedimentation rate and C reactive protein, uric acid, cholesterol
and lactate dehydrogenase.
Microscopic study of the biopsy showed an intraepidermal blister
containing neutrophils. A cavitated suppurative granuloma was
found, affecting the dermis and subcutis. The wall of the granuloma
was composed of dense fibrous tissue. Both in the blister and in
the granuloma, numerous pigmented yeast-like structures and
pigmented hyphae were found. These fungal structures were positive
with Masson-Fontana and PAS stains. Using polarizing plates, no
birefringent material was found in the granuloma. The Ziehl-Neelsen
stain showed no acid fast resistant bacilli.
Fresh direct microscopic examination of the purulent exudate
revealed pseudohyphae and yeast gemming cells (figure 5). Culture of
purulent exudate and biopsy material on Sabouraud’s dextrose agar
yielded numerous fungal colonies of Exophiala jeanselmei (figure 6). The MIC
for itraconazole was 0.01 μg/mL.
The patient was treated with oral itraconazole
(200 mg/day), for two months, which delimited the lesions and
after that, a total surgical extirpation of all the lesions was
carried out. Itraconazole treatment was maintained over one year
(long term therapy due to her immunosuppressive treatment), with
total clinical response.
Discussion
Infections caused by black yeast of Exophiala spp can be included
in three categories: phaeohyphomycosis, chromoblastomycosis and
eumycotic mycetoma. Phaeohyphomycosis shows neither true
characteristic grains or granules of eumycotic mycetoma, nor
develops the sclerotic bodies present in chromoblastomycosis [2-5,
12].
The clinical presentation of phaeohyphomycosis is very
heterogeneous [2, 3, 5], as we observed in our patients. One of
them presented several crusted lesions with linear distribution on
his lower limbs, another had an isolated erythematous plaque with
some cystic elements in the surface and the last one showed
multiple abscesiform lesions on the upper limbs and buttocks.
Most patients with phaeohyphomycosis referred to in the
literature are transplant recipients [9-11]. Our cases were not
transplant recipients; nevertheless they had other causes of
immuno-depression. One patient had received systemic
corticosteroids for eighteen years due to a respiratory disease.
Another patient was in the final stage of an autoimmune disease
currently receiving low doses of systemic steroids. Case 2 was an
elderly woman without specific causes of immuno-depression.
The diagnosis of phaeohyphomycosis in our cases was made by the
histopathological exam and confirmed by mycological cultures. Optic
microscopic examination revealed pigmented hyphae and granuloma
formation in the dermis and subcutis, epidermal involvement in case
3 was also present. These findings are in concordance with Ronan et
al. [13]. They described three histopathological patterns in
primary phaeohyphomycosis: an epidermal pattern with parakeratosis,
irregular epidermal hyperplasia with dermal and epidermal
microabscesses. The second pattern shows intradermal multi-located
cystic structures and the third one is a well-defined dermal
unilocular cyst.
The microbiological diagnosis can be difficult and it requires
expert interpretation because these fungi are common soil
inhabitants and could be considered as contaminants. In one of our
cases the direct fresh examination of purulent secretion revealed
dark septate hyphae and globular rosary-like structures that
suggested a dematiaceous fungus. In all of our patients the culture
after seven days of incubation of purulent exudate at 30 °C in
Sabouraud dextrose agar medium yielded elevated mucous greenish
black colonies with black reverse. Microscopic examination revealed
long, inflated and subglobose to broadly ellipsoidal yeast-like
cells, suggestive of the immature phase of E. jeanselmei. The slide
culture on Sabouraud dextrose agar medium after 15 days of
incubation at 30 °C produced septate hyphae with tubular and
rocket-shaped annelids that typically tapered to form a narrow
elongated tip. Ellipsoidal conidia were produced from the
annelides. These conidia, normally one-celled, were found in
clusters at the apices of annelides or at the sides of the
conidiophores (figure
5). The colony morphologies and the microscopic
characteristics of young and mature cultures allowed us to identify
the isolations as E. jeanselmei.
Antifungal sensitivity was performed with the fungi isolated in
cases 2 and 3 with the commercial system “sensititre yeast one
Y05”® and revealed very low MIC values to
itraconazole.
As other authors found, we obtained good clinical results with
this drug in two cases [14, 15]. In case 2, as the patient did not
keep to the treatment, we were forced to use terbinafine [16-18] as
an alternative therapy.
In summary, we present three cases of phaeohyphomycosis with
three different clinical presentations, not in transplant recipient
patients. Good responses were obtained with surgical and antifungal
treatment (oral itraconazol or terbinafine).
Acknowledgements
Financial support: none. Conflict of interest: none.
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