Welcome to the blog! My name is Joseph Lucas, and I am a graduate student at the Biology Department of Western Illinois University. My research at WIU involves the development of a model of artificial gene transfer in the bacterial organism Leuconostoc citreum, in order to study the genes it used to manufacture a set of unique complex carbohydrates. Over the course of our Medical Mycology class with Dr. Andrea Porras-Alfaro, we were given the opportunity to research and write a blog about a medically significant fungal disease of our choice, and I decided upon Chromoblastomycosis, a fungal disease of the skin. I hope you find it interesting!
Chromoblastomycosis
What
is Chromoblastomycosis?
Chromoblastomycosis is a fungal disease normally confined
to the skin, primarily occurring in tropical and subtropical climates,
though cases in locations such as the United Kingdom have been reported.[1]
Diagnosis is often difficult, as the symptoms often resemble a variety of
different skin diseases, such as squamous cell carcinoma.[2] The
disease is caused by a variety of fungal pathogens, but the primary two
causative species are Cladophialophora
carrionii and Fonsecaea pedrosoi.
Causative
Agents: Cladophialophora carrionii
and Fonsecaea pedrosoi
The most common cause of Chromoblastomycosis is the Ascomycota
fungus Fonsecaea pedrosoi, a darkly
pigmented, saprophytic fungus.[3] It primarily appears as a
filamentous mold in its usual habitat, usually decaying plant matter, but
exhibits in vivo dimorphism when it
infects humans; as opposed to its usual filamentous appearance, the fungus
produces rounded structures called sclerotia that are visible in biopsies of
infected tissue.[3,4] Macroscopically, colonies of Fonsecaea are filamentous and grow
slowly, generally over the course of two weeks, and appear olive green near the
edges, darkening to near black at the center.[4] When examined
microscopically, the hyphae are septate, with erect, pale-brown conidiophores.[4]
The conidia themselves are elongated, usually 1.5 – 2.5 microns wide and 3 – 6
microns long, and are produced by a variety of distinct processes involving the
production of secondary conidia from primary conidia.
 |
| Fig. 1: Conidiophore of F. pederosoi. Note the primary conidia attached to the main hyphal stalk, and producing secondary conidia. |
Cladophialophora
carrionii is the next most common cause of chromoblastomycosis. It is
ubiquitous in arid areas of South America, and, like Fonsecaea pedrosoi, is a darkly pigmented, saprophytic fungus.[5]
Colonies of this fungus are generally wooly and darkly colored, more so at the
center than the edges, and grow fairly rapidly in comparison to F. pedrosoi.[6] The
microscopic feature of the fungus are similar to F. pedrosoi, such as darkly pigmented septate hyphae, but differs
from it in regards to the conidia; whereas F.
pedrosoi produces primary conidia that then produce secondary conidia, C. carrionii simply produce unicellular
primary conidia, and there is no distinction between vegetative hyphal strands
and conidiophores.[6] The conidia themselves are lemon-shaped and
very elongated, usually 4.5 - 6 microns long by
2 – 3 microns wide, and exhibit extensive branching.[6]
 |
| Fig. 2: Conidiophore of C. carrionii. Note the long chains of lemon-shaped conidia. |
Symptoms
and Epidemiology
Symptoms of chromoblastomycosis are usually not
life-threatening, but can be disfiguring if the disease is allowed to progress
from an extended period of time without treatment, as it primarily affects the skin
and subcutaneous tissues.[7] The primary symptom is a chronic
infection of the skin, which produces a crusted or ulcerated lesion that slowly
grows as the fungus expands its habitat, and be appear in a range of colors,
from a flaking white to a black that looks similar to necrosis.[8]
Biopsies taken from this lesion, when examined microscopically, will yield
sclerotic bodies characteristic of the disease.[8]
 |
| Fig. 3: Chromblastomycosis lesion on the arm of a 9 year-old Indian child (Pradeepkumar & Joseph, 2011). |
 |
| Fig. 4: Histopathology sample displaying a fungal sclerotia characteristic of the disease, often referred to as a, "copperpenny body." (Roy, Das,& Deka, 2013). |
C. carrionii and F. pedrosoi Taxonomy[9]
Phylum:
Ascomycota
Class:
Eurotiomycetes
Order:
Chaetothyriales
Family:
Herpotrichiellaceae
Geographic
Distribution and Habitat
Both C. carrionii
and F. pedrosoi are primarily
distributed in the arid regions of Central and South America, typically
residing in soil and dead vegetative material[10]. For this reason,
commonly infected demographics include children, as well as adults whose work
involved working with these materials, especially agricultural workers.[10]
Similar
Species
Both C. carrionii and F. pedrosoi resemble a variety of
darkly pigmented fungi macroscopically, including fungi of the genus Cladosporium, another pathogenic fungus
that causes skin lesions.[11] For this reason, it is necessary to
microscopically examine samples taken and cultured from potential
chromoblastomycosis patients, searching for specific conidia and sclerotia.
Diagnosis
and Treatment
Making a diagnosis of chromoblastomycosis requires the assembly
of several different characters, as the lesions symptomatic of the disease are
highly diverse in nature, and can be easily confused with those of other
infections.[12] To begin a diagnosis, a skin scraping is taken,
treated with 10% KOH solution and stained, usually with methanamine silver.
This is followed by microscopic examination; in cases of chromoblastomycosis,
this usually reveals the presence of round, brown-pigmented sclerotia in the
tissue.[13] This should be supplemented with culturing of tissue biopsies on solid media,
such as Sabouraud’s Dextrose Agar (SDA).
Treating cases of chromoblastomycosis depends on the
severity of the infection. Minor cases can be treated by excision of infected
tissue or by application of topical antifungals, while more severe infections
require treatment with systemic antifungal drugs, such as itraconazole or
terbinafine [14].
Case
Studies
1 This case involved a 9 year old boy from
the town of Andhra Pradesh in India, who came to the hospital with a large,
dark lesion on his left arm, which was reported to have been present for 18
months, starting as a small nodule and increasing in size over time. Due to
these symptoms he was initially diagnosed with cutaneous tuberculosis and
treated with the appropriate drugs, but showed no improvement over the next
year and a half. The patient’s history was surprisingly tame: no prior lesions
had been observed, and a physical revealed no additional abnormalities or
malnutrition. Tests performed on biopsies taken from the lesion were negative
for most bacteria, however, deeper samples revealed small, round, golden-brown
structures present in the tissue, an indicator of chromoblastomycosis.
Additional tests were performed, all providing negative results, except for
culturing the tissue on Sabouraud’s dextrose agar supplemented with
antibiotics. This media revealed a slow growing fungus on the ninth day of
incubation, maturing over the next two weeks. The fungus was fuzzy and
grey-green, gradually changing to olive green as it grew. Microscopic
examination, as well as growth and metabolic tests, led doctors to identify the
fungus as Cladophialophora carrionii.
The patient was treated with the antifungal drugs itraconazole and terbinafine
for two months, and was negative for the fungus after treatment[8].
2
This case involves a 55 year old
agricultural worker, who was admitted to the hospital with a large plaque
extending from the ankle to mid-thigh of his left leg. The plaque was scaly,
with defined edges, and covered in small black ‘dots.’ His medical history was
largely unremarkable, save for a diabetes mellitus diagnosis when he was 40. The
plaque had been previously treated topically with ointments containing
itraconazole, fluconazole, and terbinafine, but none of these led to any real
improvements. Biopsies of the plaque were taken, and while no cultures were
able to grow any fungus, staining and microscopic examinations of the tissue
revealed darkly pigmented fungal cells. The combination of microscopic
observations and clinical manifestations led to a diagnosis with severe
Chromoblastomycosis. The patient was treated with oral itraconazole (400 mg
daily), and after two months of treatment, there had been significant
improvement of the lesion. By 12 months, the lesion was completely healed.[15]
Works
Cited
1.
Bhagwat, P., Tophakhane, R., Kudligi,
C., & Noronha, T. (2010). Multiple asymptomatic verrucous plaques over the
legs. Indian Journal of Dermatology, Venereology and Leprology, 76(1), 86.
doi:10.4103/0378-6323.58707
2.
Roy, A. D., Das, D., & Deka, M. (2013).
Chromoblastomycosis - A clinical mimic of squamous carcinoma. The Australasian
Medical Journal, 6(9), 458–460. doi:10.4066/AMJ.2013.1806
3.
Nimrichter, L., Cerqueira, M. D.,
Leitão, E. A., Miranda, K., Nakayasu, E. S., Almeida, S. R., … Rodrigues, M. L.
(2005). Structure, Cellular Distribution, Antigenicity, and Biological
Functions of Fonsecaea pedrosoi Ceramide Monohexosides. Infection and Immunity,
73(12), 7860–7868. doi:10.1128/IAI.73.12.7860-7868.2005
4.
“Fonsecaea spp.” Doctorfungus.org. Last
updated January 27th 2007. Accessed April 1st 2014. <http://www.doctorfungus.org/thefungi/Fonsecaea.php>.
5.
Mouchalouat, M. de F., Galhardo, M. C.
G., Fialho, P. C. M., Coelho, J. M. C. de O., Zancopé-Oliveira, R. M., &
Valle, A. C. F. do. (2008). Cladophialophora carrionii: a rare agent of
chromoblastomycosis in Rio de Janeiro State, Brazil. Revista Do Instituto de
Medicina Tropical de São Paulo, 50(6), 351–353.
doi:10.1590/S0036-46652008000600008
6.
“Cladialophora spp.” Doctorfungus.org.
Last updated January 27th 2007. Accessed April 1st 2014.
<http://www.doctorfungus.org/Thefungi/cladophialophora.php>.
7.
N Namratha, S. N. (2010).
Chromoblastomycosis due to Cladosporium carrionii. Journal of Laboratory
Physicians, 2(1), 47–8. doi:10.4103/0974-2727.66704
8.
Pradeepkumar, N. S., & Joseph, N. M.
(2011). Chromoblastomycosis caused by Cladophialophora carrionii in a child
from India. The Journal of Infection in Developing Countries, 5(07), 556–560.
doi:10.3855/jidc.1392
9. http://www.indexfungorum.org/
10.
De Hoog, G. S., Nishikaku, A. S.,
Fernandez-Zeppenfeldt, G., Padin-Gonzalez, C., Burger, E., Badali, H., … van
den Ende, A. H. G. G. (2007). Molecular analysis and pathogenicity of the
Cladophialophora carrionii complex, with
the description of a novel species. Studies in Mycology, 58, 219–234.
doi:10.3114/sim.2007.58.08
11.
“Cladosporium spp.” Doctorfungus.org.
Last updated January 27th 2007. Accessed April 1st 2014. < http://www.doctorfungus.org/thefungi/Cladosporium.php>.
12.
Queiroz-Telles, F., Esterre, P.,
Perez-Blanco, M., Vitale, R. G., Salgado, C. G., & Bonifaz, A. (2009).
Chromoblastomycosis: an overview of clinical manifestations, diagnosis and
treatment. Medical Mycology, 47(1), 3–15. doi:10.1080/13693780802538001
13.
“Chromoblastomycosis”
mycology.adelaide.edu.au. University of Adelaide. Last updated 2014. Accessed
April 2nd 2014. <http://www.mycology.adelaide.edu.au/Mycoses/Subcutaneous/Chromoblastomycosis/http://www.doctorfungus.org/thefungi/Cladosporium.php>.
14.
“Chromoblastomycosis.” Doctorfungus.org.
Last updated January 27th 2007. Accessed April 2nd 2014.
<http://www.doctorfungus.org/mycoses/human/other/chromoblastomycosis.php>.
15.
Antonello, V. S., Silva, M. C. A. da,
Cambruzzi, E., Kliemann, D. A., Santos, B. R., & Queiroz-Telles, F. (2010).
Treatment of severe chromoblastomycosis with itraconazole and 5-flucytosine
association. Revista Do Instituto de Medicina Tropical de São Paulo, 52(6),
329–331. doi:10.1590/S0036-46652010000600008
