Fungal Melanonychia: Ungual Phaeohyphomycosis caused by Botryosphaeria dothidea

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Advances in dermatology and venereology Acta Dermato-Venereologica
SHORT COMMUNICATION
Acta Derm Venereol 2017; 97: 765–766
This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta
Journal Compilation © 2017 Acta Dermato-Venereologica.
doi: 10.2340/00015555-2647
765
The phaeoid fungus Neoscytalidium dimidiatum and a
dermatophyte Trichophyton rubrum are the most fre-
quently isolated agents causing fungal melanonychia,
followed by the phaeoid fungi of the genera Alternaria
and Exophiala (1, 2). Phaeohyphomycosis is an um-
brella term describing infections in humans and other
animals characterized primarily by the development of
dark-coloured hyphae that are caused by phaeoid fungi.
The term “phaeohyphomycosis” encompasses broad
mycotic infections, regardless of the site of the lesion;
the pattern of tissue response, granuloma, or abscess; or
the taxonomy of the aetiological agents (3). We describe
here a classic example of ungual phaeohyphomycosis.
CASE REPORT
An 82-year-old retired Japanese farmer with chronic heart failure
and hemiparesis noticed a black-pigmented area on his right
thumbnail that had been present for 6 months. His internist (KS)
considered the possibility of malignant melanoma. Upon presen-
tation in February 2016, the nail was thickened and rough with a
greyish-white surface, and black pigmentation was observed from
its centre to the proximal side. Hutchinson’s sign was not observed
(Fig. 1a). The discoloured area accounted for 91% of the entire
nail plate (Image J version 1.48; National Institutes of Health,
Bethesda, MD, USA). Dermoscopy (Handyscope connected to an
iPhone 6, FotoFinder, Bad Birnbach, Germany) revealed that the
distal three-fths of the nail plate showed a whitish scaly area with
random reection and intermingling irregular black dots, while
the proximal one-fth showed a normal nail plate. Between these
2 areas, a black homogenous area and a partially grey granular
area were observed (Fig. 1b).
Direct microscopy revealed branching brown septate hyphae
(Fig. 2a), and haematoxylin and eosin and periodic acid-Schiff
staining revealed black septate hyphae in the nail plate. The thick
cell wall appeared to be double contoured (Fig. 2b). Plate culture
on potato dextrose agar after 7 days at 30°C showed a greyish-white
woolly colony with coal-black pigmentation on the reverse (Fig. 2c,
d). Slide culture showed pigmented broad and unpigmented narrow
branching hyphae and intercalary and acropetal chlamydoconidia
measuring up to 40 μm (Fig. 2e). The sequence of the internal
transcribed spacer 1 region of the ribosomal RNA gene from the
nail and isolate had 99% homology to the Botryosphaeria dothidea
type strain CBS 115476 (accession: KF766151) (4). Based on
the morphological characteristics and gene analysis results, we
diagnosed the patient with ungual phaeohyphomycosis due to B.
dothidea (Moug. ex Fr.) Ces. & De Not. The minimum inhibitory
concentrations for the isolate were as follows: amphotericin B, 0.25
µg/ml; enaconazole (EFCZ), 1.0 µg/ml; uconazole, > 64 µg/ml;
5-uorocytosine, 2 µg/ml; itraconazole, > 16 µg/ml; micafungin,
0.25 µg/ml; miconazole, 0.25 µg/ml; terbinane, 0.5 µg/ml; and
voriconazole, 0.03 µg/ml. Nail opacity was reduced to 74% and
32% of the nail surface after 1 and 4 months, respectively, of topical
application of 10% EFCZ solution (Fig. 1c). The discoloration
disappeared with negative conversion of the fungi after 7 months.
The patient showed no recurrence of fungal infection during a
3-month follow-up, as of December 2016.
Fungal Melanonychia: Ungual Phaeohyphomycosis caused by Botryosphaeria dothidea
Hiromitsu NOGUCHI
1,2
, Masataro HIRUMA
2
, Tadahiko MATSUMOTO
2
, Rui KANO
3
, Masaru TANAKA
4
, Takashi YAGUCHI
5
,
Kazuhiro SONODA
6
and Hironobu IHN
7
1
Noguchi Dermatology Clinic, 1834-1 Namazu, Kashima-machi, Kamimashiki-gun, Kumamoto 861-3101,
2
Ochanomizu Institute for Medical
Mycology and Allergology, Tokyo,
3
Department of Pathobiology, Nihon University School of Veterinary Medicine, Kanagawa,
4
Department of
Dermatology, Tokyo Women’s Medical University Medical Center East, Tokyo,
5
Division of Bio-resources, Medical Mycology Research Center,
Chiba University, Chiba,
6
Division of Internal Medicine, Yatsuda Hospital, Kumamoto, and
7
Department of Dermatology and Plastic Surgery,
Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. E-mail: derma@nogcli.jp
Accepted Mar 15, 2017; Epub ahead of print Mar 15, 2017
Fig. 1. Clinical characteristics of the thumb nail. (a) Clinical image at
presentation. Melanonychia without Hutchinson’s sign. (b) Dermoscopic
image showing a black homogenous area and coarse granules proximally.
(c) Findings after 4 months of topical application of 10% enaconazole
solution. The opacity ratio decreased from 91% to 32% during that time.
Fig. 2. Mycologic characteristics. (a) Direct microscopic examination
revealed branching black hyphae (KOH preparation, original magnication
×400). (b) Septate black hyphae in the nail plate (periodic acid-Schiff
staining ×400). (c, d) Plate culture showed a greyish-white woolly colony
with a coal-black pigmentation on the reverse. (e) Slide culture showed
pigmented broad and unpigmented narrow hyphae and chlamydoconidia.
(Lactophenol Cotton Blue staining ×400).

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DISCUSSION
Botryosphaeria dothidea was rst described as Sphaeria
dothidea Moug. in 1823. The type species of the genus
(family Botryosphaeriaceae, order Botryosphaeriales,
class Dothideomycetes, phylum Ascomycota) is B. dothi-
dea. Fungi in the order Botryosphaeriales are the most wi-
despread and important plant-pathogens associated with
twig, branch, and stem cankers; tip and branch dieback;
fruit rot; blue stain; and plant death (5). To date there have
been no reports of B. dothidea infection in humans or
lower animals, while N. dimidiatum is the most frequent
non-dermatophyte and non-Candida pathogen causing
onychomycosis in tropical and subtropical regions (6).
A survey in Brazil showed that the typical symptom as-
sociated with onychomycosis caused by N. dimidiatum
was a lateral-distal and lateral-subungual lesion in the big
toenail, and melanonychia accounted for 66.6% (20/30)
of all cases. It developed in 27.2% (3/11) of Caucasians
and 89.4% (17/19) of non-Caucasian individuals (7). The
sequence of the internal transcribed spacer 1 region of
the ribosomal RNA gene from the isolate and the nail
in our case had 95% homology with the N. dimidiatum
type strain CBS 499.66 (accession: FM211432) (4). Our
case occurred on the Kyushu island of Japan, which is
located in the temperate region at 32° north latitude with
a mean temperature of 17.2
± 0.5°C. The annual mean
temperature in the Northern hemisphere has increased
by 0.85°C during the past 30 years (1983–2012) (8).
The incidence of B. dothidea infections might therefore
increase gradually even in temperate regions.
Although pigment cells exist in both the nailbed and
the nail matrix, melanoma derived from the nailbed has
an amelanotic tendency. It is important to differentiate
melanonychia arising in the proximal part of the nail
from malignant melanoma even if Hutchinson’s sign is
not noted (9). The characteristic dermoscopic images of
fungal melanonychia are homogeneous pigmented coarse
granular lesions with ne black granules of a diameter
of 0.1 mm or less (9), which were useful for ruling out
a diagnosis of malignant melanoma. The clinical ap-
pearances of longitudinal melanonychia were similar
to those caused by Phialophora species (10) and were
different from those caused by T. rubrum presenting
bundle-forming longitudinal lines with a brownish or
yellow element (11).
Because onychomycosis caused by N. dimidiatum is
refractory and resistant to itraconazole and terbinane
(6), the conventional therapy was expected to be inef-
fective against B. dothidea infection. In this case, topical
application of 10% EFCZ solution was effective. EFCZ
is a novel triazole antifungal agent that has good human
nail permeability and retention properties (12, 13).
Because of its broad spectrum of antifungal activities
(14), EFCZ is a promising option in the treatment of
non-dermatophyte onychomycosis including ungual
phaeohyphomycosis (15).
ACKNOWLEDGEMENTS
This research was partially supported by the Research Program
on Emerging and Re-emerging Infectious Diseases from the Japan
Agency for Medical Research and Development, MAED.
The authors declare no conicts of interest.
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