The Aspergillus Niger Causing Eumycetoma in an
Immunocompetent Host: Report of a Case and Review of the Literature
YousufAbd Mallick,1 Nausheen Yaqoob2
1: Dermatology Unit, the Indus Hospital Karachi, Pakistan.
2: Pathology Unit, the Indus Hospital Karachi, Pakistan.
Correspondence
to Dr. YousufAbdMallickEmail: dryousuf2006@yahoo.com
ABSTRACT
Mycetoma is a chronic granulomatous
infection of skin and subcutaneous tissues. It is a neglected disease with
severe physical and psychological comorbidity burden as many cases end up with
amputations. Proper diagnosis with tissue culture is lacking because of
unavailability of facilities in remote areas. Eumycetoma by different Aspergillus
species has already been reported in the literature for decades. But here,
weare reporting a case of eumycetoma caused by Aspergillus niger, which is the
first ever case-report to the best of our knowledge and search. Treatment with
voriconazole 400 mg/day was successful without any major side-effects, and
saved patient from amputation.
Keywords: Mycetoma,
Eumycetoma, Aspergillusniger, Voriconazole, dot-in-circle sign.
INTRODUCTION
Mycetoma is an uncommon, chronic
granulomatous infection of skin and subcutaneous tissues with involvement of
underlying fasciae and bones in majority of cases. The disease has a classical
triad which consists of formation of multiple draining sinuses, presence of
discharging grains and tumefaction of affected tissues.1 Feet are
the most common site involved. Causative agents are divided into two groups;
actinomycetes and fungi. When it is caused by a fungus it s termed as
eumycetoma, while the one caused by actinomycete is called as actinomycetoma.
Eumycetoma by different Aspergillus species in immunocompetent and
immunocompromised patients is not new but we are reporting a case of eumycetoma
caused by Aspergillus niger, which is the first ever case-report to the best of
our knowledge and literature search.
CASEREPORT
A 49-year-old male, farmer by
profession, presented to the Dermatology department of The Indus Hospital,
Karachi with 8-year history of formation of nodules and recurrent discharging
sinuses in his right foot. He had history of trauma to right foot 8 years back
in fields. After 2-3 months of trauma he noticed formation of nodules on sole
of right foot. These ruptured to release pus and black-coloured grains.
Later-on similar nodules and sinuses were formed on dorsum and medial aspect of
the foot. He received multiple treatments from different places including
terbinafine, itraconazole, fluconazole, and co-trimoxazole. Minimal improvement
was noticed and condition relapsed as soon as the treatment was stopped. On
examination, he had firm nodules and active discharging sinuses (Figures
1a& 1b). Spores were extracted from sinuses and nodules, and examined under
microscope. Fungal hyphae were seen on KOH mount. Deep skin biopsy and cultures
were sent to laboratory and terbinafine 500 mg/day was started. On examination
all spores were black in colour; small-sized, soft & fragile, and surface
was smooth. This is in contrary with typical black-spores of Madurella species
which are rough, hard and slightly larger than spores which we extracted,
although our prime diagnosis was eumycetoma with one of the Madurella species.
Biopsy report showed hyperplastic
stratified squamous epithelium along with hyperkeratosis and parakeratosis.
Dermis showed dense lymphoplasmacytic infiltrate along with hyaline budding,
septate fungal hyphae and spores surrounded by multinucleated giant cell
reaction, neutrophils and eosinophils (Figure 2). These colonies were
highlighted by special stain; Periodic acid-Schiff (PAS) stain. Features were
suggestive of eumycetoma due to Aspergillus species. Later-on culture also
showed Aspergillus niger species. A second culture also confirmed the
same species in Potato dextrose agar culture medium.
Routine labs and sugars were normal.
Hepatitis B, C and HIV serology were negative. After 1 month when cultures
confirmed the species and patient had no improvement on terbinafine 500 mg/day,
we decided to switch to Voriconazole 400 mg/day. MRI at the start of therapy
showed dot-in-circle sign in right medial cuneiform bone. Rest of the bones
were spared. Within 1 month his sinuses were started to heal. So, we continued
the drug in the same dose. After 6 months of treatment he became culture
negative, all sinuses were healed, edema was reduced and he was pain free. We
continued voriconazole in same dose for 12 months. Repeat MRI after 1 year of
therapy did not show any enhancement or active signs of inflammation in medial
cuneiform bone.
During treatment, he reported repeated
flu like symptoms, oral ulcers, burning in eyes and gastrointestinal upsets but
his all labs were remained under control and no serious side effect from
voriconazole was reported. After completing one-year therapy he was symptom
free and clinically there was no finding besides post inflammatory
hyperpigmentation (Figures 3a & 3b). So, his therapy was discontinued. 6
months after discontinuation of therapy he was symptom-free and no relapse was
appreciated.
DISCUSSION
Mycetoma
(Madura foot) was first described by Gill in 1842 in Madura district of Tamil
Nadu in Southern India.2 It commonly presents between 20 to 50 years
of age, with a male to female ratio of 2.2:1.3 Foot is the
predominant site involved that s why the term Madura foot was given by Gill.2
Mycetoma foot is prevalent in almost all parts of the world, but the highest
incidence is reported between latitude 15 S and 30 N, the so called
mycetoma-belt .4 Depending upon the aetiology, the disease is
classified into two types; actinomycetoma and eumycetoma. The eumycetoma is
classified into black grain eumycetoma and white grain eumycetoma. The black
grain eumycetoma is most commonly caused by Madurellamycetomatis,
Madurellagrisea, Exophialajeanselmei, and Curvularia
geniculate species.The white grain eumycetoma is caused by various
species from genus Acremonium, Pseudoallescheria,
Aspergillus, Fusarium and Scedosporium.4
Aspergillus fungi are ubiquitous, opportunistic, filament forming
moulds, comprises of over 180 different species. These are globally distributed
and present in water, soil, air, plants, dust, fields, deserts etc.5Many
species are responsible for causing infections in humans. Aspergillus niger
(also known as Black Mould) belongs to the Section Nigri which includes 15
related black-spored species which shared many physical and chemical
properties.
In the literature Aspergillus fumigatus, A. flavus, A. nidulans,
A. terreus, and A. ustus had been reported with human eumycetoma infections.1,5-11
However, Aspergillus niger is reported to be responsible for mycetoma of
maxillary sinus and lungs, but not outlined as a cause of eumycetoma foot to
the best of our literature search and knowledge.12-13
Eumycetoma due to Aspergillus species is considered as most
difficult to treat as most species of Aspergillus are naturally azoles and
terbinafine resistant.11The same occurred in our case. He received
many treatments but all in vain. The decision to start voriconazole was made
after thorough literature (medical, surgical, paediatric, oncology and
infectious diseases) search for drugs used against Aspergillus infections and
especially A. niger infections. Our patient responded very well to voriconazole
and his foot was saved from amputation. He experienced no serious side effects
and his labs were always remained in normal limits during therapy.
CONCLUSION
Mycetoma is a disease mostly
concentrated in tropical and subtropical countries. Detection of organism by
tissue culture and PCR analysis is cornerstone in the management of these
cases. Early referral to tertiary care centers, identification of species by
proper tissue culture and adequate treatment might decrease the disease-related
morbidity in mycetoma cases. Furthermore; this case also enlarges the list of
organisms from Aspergillus group which are causing human eumycetoma.
Figure
1 a: Nodule was excised for biopsy and cultures, showing black grain at the
base.
Figure
1 b: Sinus showing discharge of black grains
Figure 2: Septate fungal hyphae and
spores with hyaline budding surrounded by multinucleated giant cells,
neutrophils, eosinophils and lymphocytes
Figures
3a & 3b: Showing complete recovery and healing of all sinuses after
12-months therapy with voriconazole
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