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Journal of Clinical Microbiology, March 1998, p. 708-715, Vol. 36, No. 3
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
U.S. Case Report of Cerebral Phaeohyphomycosis
Caused by Ramichloridium obovoideum (R. mackenziei):
Criteria for Identification, Therapy, and Review of Other
Known Dematiaceous Neurotropic Taxa
Deanna A.
Sutton,1,*
Malcolm
Slifkin,2
Robert
Yakulis,2 and
Michael
G.
Rinaldi1,3
Fungus Testing Laboratory, Department of
Pathology, University of Texas Health Science Center at San
Antonio1 and
Audie L. Murphy Division,
South Texas Veterans Health Care System,3
San Antonio, Texas 78284, and
Department of Laboratory
Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania
15212-47722
Received 21 August 1997/Returned for modification 24 October
1997/Accepted 25 November 1997
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ABSTRACT |
We report a case of cerebral phaeohyphomycosis in a 36-year-old
male caused by the neurotropic fungus Ramichloridium
obovoideum (Matushima) de Hoog 1977 (Ramichloridium
mackenziei Campbell et Al-Hedaithy 1993). This man resided in the
Middle East, where the fungus appears to be endemic and, possibly,
geographically restricted, since all previous reports of brain
abscesses due to this organism have been for patients indigenous to
this area. As a servant of the Saudi Arabian royal family, he appeared
in the United States seeking treatment for chronic weight loss,
fatigue, decreased memory, and a more recent 2-week history of
right-hand weakness which worsened to involve the entire right upper
extremity. On the day prior to his admission, he had a focal motor
seizure with rotation of the head and eyes to the right, followed by
secondary generalization. A computerized tomogram showed a
ring-enhancing hypodense lesion in the left parietal subcortical region
with associated edema and mass effect. Diagnosis of a fungal etiology was made following a parietal craniotomy and excisional biopsy by
observation of septate, dematiaceous hyphal elements 2 to 3 µm in
width on hematoxylin-and-eosin-stained sections from within areas of
inflammation and necrosis. Culture of the excised material grew out a
dematiaceous mould which was subsequently identified as R. obovoideum. At two months postsurgery and with a regimen of 200 mg of itraconazole twice a day, the patient was doing well and returned
to Saudi Arabia. His condition subsequently deteriorated, however, and
following a 7-month course of itraconzole, he expired. We use this case
to alert clinicians and personnel in clinical mycology laboratories of
the pathogenicity of this organism and its potential occurrence in
patients with central nervous system signs and symptoms who have
resided in the Middle East and to review and/or compare R. obovoideum with other neurotropic, dematiaceous taxa and similar
nonneurotropic, dematiaceous species.
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INTRODUCTION |
The numbers and types of saprobic,
opportunistic, and dematiaceous moulds that have been documented as
etiologic agents of phaeohyphomycosis continue to escalate.
Clinical presentations may include superficial, cutaneous,
subcutaneous, and systemic disease. Dematiaceous fungi that occur in
compromised hosts may go on to disseminate hematogenously, inciting
disease in various organs. Some that disseminate appear neurotropic,
i.e., have a predilection for central nervous system (CNS) tissue,
where they may localize, causing brain lesions and/or abscesses. These
neurotropic organisms are frequently thermotolerant or thermophilic,
growing at 40°C or higher. Dematiaceous filamentous taxa known to be
neurotropic include the hyphomycetous fungi Cladophialophora
bantiana (Saccardo) de Hoog, Kwon-Chung et McGinnis (4, 12,
20, 24, 25, 30, 44, 52), Exophiala dermatitidis (Kano)
de Hoog (Wangiella dermatitidis McGinnis) (21, 23, 24,
27, 35, 46, 52), and Ochroconis gallopavum (Cooke) de
Hoog (24, 47, 51, 52), as well as the dematiaceous
ascomycete Chaetomium atrobrunneum Ames (1, 39).
Bipolaris spicifera (Bainer) Subramanian (5, 24,
53) and Bipolaris hawaiiensis (M. B. Ellis)
Uchida et Aragaki (24, 31, 41) may also invade the CNS via
paranasal sinus extension. Additional dematiaceous agents
incriminated include Rhinocladiella atrovirens
Nannfeldt (10, 24), Curvularia pallescens Boedijn
(16, 24, 26), and Fonsecaea pedrosoi (Brumpt)
Negroni (2, 17, 18, 24, 52). Most of these species
have a rather widespread distribution and are encountered
in various ecological niches. Based on cases previously reported
as either Ramichloridium obovoideum or
Ramichloridium mackenziei, however, this etiologic agent appears to be geographically restricted to the Middle
East (7, 22, 28, 32). Nonneurotropic species sharing
macroscopic and microscopic morphologies similar to those of
R. obovoideum include Ramichloridium schulzeri
Saccardo de Hoog (8, 9, 13, 14, 40), Rhinocladiella
aquaspersa (Borelli) Schell et al. (8, 42), and
Veronaea botryosa Ciferri et Montemartini (3, 9,
35). A comparison of culture characteristics,
microscopic morphologies, and in vitro susceptibilities may aid in
differential diagnosis for patients with CNS signs and/or symptoms of a
presumed, dematiaceous fungal etiology.
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MATERIALS AND METHODS |
Case report.
The patient was a 36-year-old male servant of
the Saudi Arabian royal family who presented at the Allegheny General
Hospital in Pittsburgh, Pa., in May of 1995 with a 2-week history of
right-hand weakness which worsened to involve the entire right upper
extremity. On the day prior to admission, he had a focal motor seizure
with rotation of the head and eyes to the right, followed by secondary generalization.
His past medical history was significant for stage IIIb
mixed-cellularity Hodgkin's disease diagnosed by biopsy of the left axillary lymph node in 1983. The patient was treated with alternating cycles of MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) until complete remission was achieved. In 1986, the patient suffered a relapse which required six cycles of MOPP and ABVD.
The patient relapsed again, was treated with CMVP-16 (cyclophosphamide, methotrexate, etoposide), and had been in complete remission since 1987. Past medical history was also significant for schistosomiasis as
a child and chronic hepatitis B with portal hypertension, hepatomegaly, and splenomegaly. Since 1993, the patient had noticed a 10- to 12-kg
weight loss, was chronically fatigued and apathetic, and had a
decreased memory.
Upon admission on 6 May 1995, the patient was fully conscious, had a
bitten tongue, normal fundi, and normal visual fields. There was
increased weakness in the right upper extremity which was more
pronounced distally than proximally, hyperactive deep tendon reflexes,
and normal sensation. During his hospital stay, there was deterioration
of normal lower-extremity strength over a period of 2 weeks.
Except for hepatosplenomegaly, the remainder of the physical
examination was within normal limits. The clinical impression was of
upper neuron weakness of the right upper and lower extremities with
right focal motor seizure with secondary generalization. A
space-occupying lesion in the left midrolandic gyrus was suspected.
An electroencephalogram showed a normal pattern of waking and sleeping.
A preoperative computerized tomogram with and without
contrast showed a
ring-enhancing hypodense lesion in the left
parietal subcortical region
with associated edema and mass effect,
but no significant midline shift
(Fig.
1). Radiographically, the
diagnostic possibilities included solitary brain metastasis, high-grade
glioma, and brain abscess.
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FIG. 1.
A computerized tomogram scan with contrast showing a
ring-enhancing hypodense lesion in the left parietal subcortical region
with surrounding edema.
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Leukocyte count decreased to 3,900 per mm
3, with a normal
differential. Total amounts of protein and globulins in serum were
decreased to 5.9 and 2.25 g%, respectively. Levels of alkaline
phosphatase, gamma glutamyl transpeptidase, alanine aminotransferase,
aspartate aminotransferase, creatine phosphokinase, and lactate
dehydrogenase were 393, 108, 46, 61, 865, and 309 IU/liter,
respectively.
The serum cholesterol level was elevated to 203 mg/dl.
Chest and
dorsal spine radiographs were within normal limits.
Ultrasound
of the abdomen showed mild hepatosplenomegaly but no
enlarged
retroperitoneal or periaortic lymph nodes. Treatment of the
patient
with 100 mg of phenytoin was begun.
On 18 May, 12 days postadmission, the patient underwent a parietal
craniotomy and an excisional biopsy. At operation, an extremely
thick
capsule was encountered which, upon penetration, contained
3 cm
3 of thick, grossly purulent material. The ball of the
cavity was
dissected free of the surrounding white matter and extended
several
centimeters below the cortex. Approximately 2 by 2 by 2 cm of
white and brown tissue submitted for frozen sectioning and hematoxylin
and eosin staining showed a severe mixed acute and granulomatous
infiltrate with large areas of tissue necrosis (Fig.
2). Within
the areas of inflammation and
tissue necrosis were occasional
brown pigmented hyphal forms
approximately 2 to 3 µm in width,
with the presence of septa in some
areas. The fungal elements
were also readily apparent in
paraffin-embedded Congo red tissue
sections (Fig.
3). Although the hyphal form
predominated, there
were also moniliform elements (hyphal elements with
swellings
a regular intervals) measuring up to 4 µm in diameter at
their
widest point. These were most easily visualized in the Gomori
methenamine silver-stained sections (Fig.
4). Following histopathological
confirmation of a dematiaceous mould as the etiologic agent, a
regimen
of 200 mg of itraconazole (ITRA) twice a day (BID) was
begun.
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FIG. 2.
Brain lesions showing mixed acute and granulomatous
inflammation with hematoxylin and eosin staining. Magnification,
×300.
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FIG. 3.
Paraffin-embedded Congo red tissue sections containing
hyphal elements of R. obovoideum. Magnification,
×630.
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FIG. 4.
Gomori methenamine silver stain showing moniliform
hyphal elements of R. obovoideum. Note the moniliform
(bead-like) hyphae characteristic of agents of phaeohyphomycosis.
Magnification, ×1,200.
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The fungal culture was referred to the Fungus Testing Laboratory,
Department of Pathology, University of Texas Health Science
Center at
San Antonio (accession no. 95-1147) for identification
and
susceptibility studies.
In July 1995, 2 months postsurgery, the patient was doing well and the
weakness, involving his right arm and leg had improved
considerably. He
returned to Saudi Arabia, continuing his regimen
of 200 mg of ITRA BID.
However, his condition subsequently deteriorated,
requiring
rehospitalization. He expired on 1 January 1996, after
having received
approximately 8 months of itraconazole. The patient
did not garden and
had no occupational exposure to the soil. Interestingly,
he did walk
barefoot in the desert. He had formerly been employed
as a telephone
operator before his most recent employment as a
servant for the royal
family.
Histopathology.
Approximately 2 by 2 by 2 cm of white and
brown tissue was submitted for frozen sections and hematoxylin and
eosin and Gomori methenamine silver stains. Deparaffined histological
sections with fluorescent calcofluor white Fungi-Fluor stains
(Polysciences, Inc., Warrington, Pa.) and Congo red stains (Sigma
Chemical, St. Louis, Mo.) were also examined (48).
Mycology.
Brain tissue from the excisional biopsy was
submitted to the mycology laboratory for fungal cultures. The specimen
was plated on Sabhi and brain heart infusion agars with 5% sheep blood
(Becton Dickinson Microbiology Systems, Cockeysville, Md.), with
incubation at 30°C. These primary plates had been sealed with Shrink
Seal (Scientific Devise Laboratory, Inc., Glenview, Ill.) to maintain adequate humidity.
The isolate was referred to the Fungus Testing Laboratory, University
of Texas Health Science Center at San Antonio, San Antonio,
Tex., for
identification and susceptibility testing. The isolate
was plated onto
potato flakes agar (PFA), which was prepared in-house
(
37),
and Mycobiotic Agar (Remel, Lenexa, Kans.) at 25°C (ambient
air,
alternating daylight and darkness), at 35°C, and at 42°C
(ambient
air in the dark). Subcultures at 25 and 35°C were held
for 4 weeks,
while those at 42°C were maintained for 2 weeks.
Slide cultures,
maintained for 7 days at 25°C, were prepared on
PFA blocks and
examined in lactophenol cotton blue (Poly Scientific
Research and
Development Corp., Bay Shore, N.Y.) mounts.
Antifungal susceptibility testing.
The case isolate was
tested to determine its susceptibilities to antifungal agents. Tests
were performed by previously described macrodilution methods (34,
38). Briefly, the case isolate and the Paecilomyces
control strain (UTHSC 90-459) were grown on PFA, which was prepared
in-house, for 14 days at 25°C to induce conidial formation. Mature
PFA cultures were overlaid with sterile, distilled water, and
suspensions were made by gently scraping the colonies with the tip of a
Pasteur pipette. Heavy hyphal fragments were allowed to settle, and the
upper, homogeneous conidial suspensions were removed. Conidial
suspensions were adjusted spectrophotometrically to 95% transmittance
at 530 nm and were further diluted 1:10 in medium. Final drug
concentration ranges were as follows: for amphotericin B (AMB;
E.R. Squibb & Sons, Princeton, N.J.), 0.03 to 16 µg/ml; for
5-fluorocytosine (5-FC; Hoffmann-La Roche Inc., Nutley, N.J.), 0.125 to
64 µg/ml; for fluconazole (FLU; Pfizer, Inc., New York, N.Y.), 0.125 to 64 µg/ml; and for ITRA (Janssen Pharmaceutica, Titusville, N.J.),
0.015 to 8 µg/ml. AMB was tested in Antibiotic Medium 3 (Difco,
Detroit, Mich.); other antifungal agents were tested in RPMI-1640 with
L-glutamine and morpholinepropanesulfonic acid (MOPS)
buffer at a concentration of 165 mM and without sodium bicarbonate
(American Biorganics, Inc., Niagara Falls, N.Y.). Previously prepared,
frozen drug tubes containing 0.1 ml of drug were allowed to thaw and
were inoculated with 0.9 ml of the conidial medium suspension. A
drug-free growth control tube was included with the case isolate and
control organism. The tubes were incubated at 35°C, and MICs were
read at the first 24-h interval when growth was observed in the
drug-free growth control. MICs were defined in terms of the first tube
that gave a score of 0 (optically clear) for AMB and a score of 2 (reduction in turbidity of 
80% in contrast to the drug-free control
tube) for 5-FC, FLU, and ITRA.
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RESULTS |
Mycology.
At the Allegheny General Hospital, the mould was
first detected on Sabhi and brain heart infusion agars as small, gray,
lanose colonies at 4 days of incubation at 30°C. After 7 days of
incubation, colonies were 8 to 10 mm, lanose, and gray black. The
reverse color on Sabhi agar was gray black, with the tops of the
colonies on both media being black, woolly, and domed. The microscopic morphology, by tape and teased mounts in lactophenol cotton blue (Becton Dickinson Microbiology Systems), was described as similar to
that seen in F. pedrosoi. Often two smooth-walled and
lightly pigmented conidia were seen projecting from both sides of the relatively thick-walled rachis, giving a "Mickey Mouse" appearance (Fig. 5A). Cultures in the Fungus Testing
Laboratory on PFA at 25°C revealed colonies that were dark brown to
black with a jet-black reverse, woolly, and slow growing, reaching only
2 to 4 mm in 10 days. Six weeks of incubation at 25°C produced
colonies with a high-domed central area and a submerged margin
throughout. Growth was better at 35 than 25°C with diameters reaching
12 to 20 mm in 17 days. Growth also occurred at 42°C and on media
containing cycloheximide, although measurements were not taken. Hyphae
were septate and brown, measuring 1.3 to 2.0 µm in diameter.
Conidiophores arose at more or less right angles to the vegetative
hyphae and were not strongly differentiated from it
(micronematous). The conidiogenous areas elongated sympodially,
becoming flexous (Fig. 5B). The conidial rachis, 3 to 12 µm long by 3 to 5 µm in diameter, was somewhat larger than the lower part of the
conidiogenous cells. Relatively few conidia per fertile axis were
present. They were pale brown, ellipsoid to obovoid, single celled,
smooth, 5.85 to 8.7 µm long by 2.7 to 4.8 µm wide, with a
protuberant hilum or a flat secession scar up to 1.3 µm wide (Fig.
5C).
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FIG. 5.
(A) Cellophane tape preparation of R. obovoideum showing the "Mickey Mouse" appearance of immature,
sympodially proliferating conidiogenous cells with mostly two conidia.
Magnification by the Hoffman modulation contrast system, ×630. (B)
Conidiogenous cells of R. obovoideum with few conidia
per fertile axis. Magnification by Nomarski optics, ×920. Reprinted
from reference 50 with permission of the publisher.
(C) Numerous conidia of R. obovoideum showing a
protuberant hilum (arrow) or flat secession scar. Magnification by
Nomarski optics, ×920. Reprinted from reference 50
with permission of the publisher.
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In vitro antifungal susceptibility.
The results of in vitro
susceptibility tests, based on drug concentrations normally achievable
in patients receiving recommended dosages, indicated that the isolate
was susceptible to AMB and ITRA (19, 45). MICs were read
initially at 192 h (when growth control was first positive) and
again at 216 h (24- to 48-h intervals) were 0.5 and 1 µg/ml and
0.015 and 0.015 µg/ml, respectively. MICs of 5-FC, an antifungal
agent used primarily in combination therapy, were 8 and 8 µg/ml. FLU
MICs were 16 and 16 µg/ml, concentrations which may be achieved at
elevated dosing regimens (36). Both 5-FC and FLU MICs were
read after 192 and 216 h of incubation.
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DISCUSSION |
Case report.
Although the patient's past medical history was
significant for stage IIIb mixed-cellularity Hodgkin's disease (in
complete remission since 1987), chronic hepatitis B with portal
hypertension, hepatomegaly, and splenomegaly, and shistosomiasis as a
child, it is difficult to establish whether these conditions were
contributory to acquisition of the fungus. The patient denied any
occupational exposure to the soil, but he did walk barefoot in the
desert. Cerebral phaeohyphomycosis due to other neurotropic agents,
particularly C. bantiana, is also frequently seen in
patients without obvious (detectable), immunosuppressive, coincidental
patterns of preexisting illness and without an unambiguous occupational
predisposition, although culturally proven cases do have a male-to
female ratio of about 3:1 (12, 24). One exception appears to
be the relationship between preexisting Nocardia asteroides
and phaeohyphomycotic brain abscesses due to C. bantiana
(24, 30, 32, 43). In the 8 cases of R. obovoideum referenced here, in which the sex of the patient was
known, the male-to-female ratio was 1:1.
Therapy.
Cerebral phaeohyphomycosis is one of the most serious
clinical manifestations caused by dematiaceous fungi and has a high degree of morbidity and mortality, requiring early and aggressive therapy. The patient in this case report was admitted on 6 May 1995, was diagnosed on 18 May 1995, was given an initial dose of 200 mg of
ITRA BID on 22 May 1995, and remained on this regimen until 26 December
1995, 6 days prior to expiring on 1 January 1996. Although the patient
was diagnosed rather quickly after admission, he had experienced a
weight loss of 10 to 12 kg, was chronically fatigued and apathetic, and
had had a decrease in memory since 1993. Seventeen cases of
intracranial mycoses requiring neurosurgical intervention were reviewed
by Jamjoom et al. (22). Citing a 41% mortality, they
indicated that reasons for a fatal outcome included (i) failure to
consider a fungal etiology, (ii) failure to obtain an early
tissue diagnosis because of late referral, and (iii) failure to respond
to antifungal therapy. Naim-ur-Rahman et al. reported three cases
with a 100% mortality due to rupture of recurring abscesses into the
ventricles despite adequate antifungal chemotherapy and multiple
surgical procedures (33). The fatal outcome in this patient
may have been attributed, in part, both to his seeking medical
attention late in the course of the disease to possible failure of ITRA
therapy. However, he did appear to receive an adequate dosing regimen
for an isolate demonstrating in vitro susceptibility to this agent
(MICs of less than 0.015 µg/ml) (45). Although levels in
serum documenting adequate absorption of the drug were not measured,
the patient did initially respond to the drug, permitting his return
home to Saudi Arabia. ITRA, like other azole antifungals, is
fungistatic rather than fungicical and may have merely suppressed the
organism. Factors in addition to in vitro susceptibility which may have
influenced the outcome, as outlined by Rex et al., include the
pharmacokinetics of the drug, general host factors, site of infection,
and virulence of the pathogen (36). In vivo-in vitro drug
studies with other neurotropic agents, C. bantiana, E. dermatitidis, and O. gallopavum (Dactylaria
constricta var. gallopava), prior to the introduction of ITRA, suggested that the greatest protection in experimentally infected mice was offered by 5-FC followed by AMB, FLU, and
ketoconazole and that in vitro susceptibility testing had no
predictive value (11). In vivo animal studies with
R. obovoideum versus ITRA were not available at the
time of the patient's therapy.
A review by Dixon et al. of 26 cases of CNS fungal infections due to
C. bantiana suggested that the neurosurgical resection
of
the lesion, with or without antifungal therapy, was the most
important
determinant for cure and survival (
12). A resectable
lesion
was defined as a discrete mass demarcated by a peripheral
gliotic
capsule surrounding necrotic infected debris, in contrast
to abscesses
having poorly delimited margins and satellite abscesses.
Complete
resection of the lesion in this case was not thought
possible.
Antifungal susceptibility.
While standardization in antifungal
susceptibility testing has been attained for the major, clinically
significant yeasts with publication of the National Committee for
Clinical Laboratory Standards document no. M27-A (34),
standardization of susceptibility testing for filamentous fungi is only
commencing (15). Parameters previously defined for yeast
testing, with some modification, also appear to be
useful for mould testing. The case isolate in the present
study was tested by a modified M27-A method. Although standardized
antifungal susceptibility testing now permits large surveys of yeast
isolates for correlating MIC data with clinical response, such
correlations for infrequently encountered moulds are not possible,
still making empiric therapy necessary. Clinical outcomes with
R. obovoideum have been dismal, regardless of
antifungal therapy, and appear to lack correlation with in vitro data
(7).
Taxonomy and identifying features.
The genus
Ramichloridium, causing leaf-spots on banana, was first
described by Stahel (49). However, the description was invalidly published, lacking a Latin description. In 1977, de Hoog
reviewed a number of dematiaceous hyphomycetes that produce holoblastic
conidia from a sympodial proliferating axis, including Ramichloridium and Rhinocladiella (8).
These genera were separated mainly on the basis of (i) macronematous
conidiophores in Ramichloridium versus micronematous
conidiophores in Rhinocladiella and (ii) human
pathogenicity, lacking in Ramichloridium but present in Rhinocladiella species. A third, less stable characteristic
mentioned was the presence of a yellow or an orange diffusable pigment, often present in Ramichloridium but lacking in
Rhinocladiella. R. obovoideum (Matsushima) de Hoog
comb. nov. was included in Stahel's review and was originally
described as R. obovoideum. In the late 1980s, case
reports incriminating R. obovoideum as an agent
of cerebral phaeohyphomycosis emerged. In 1993 Campbell and
Al-Hedaithy published a review of eight cases due to an
organism they named R. mackenziei (Table
1) (7). Characteristics which deviated from the previously-described genus Ramichloridium
included (i) a lack of yellow or orange diffusable pigment, (ii)
conidiophores not obviously differentiated from the vegetative
hyphae, and (iii) the unambiguous human pathogenicity of the organism.
Despite these deviations, they felt the most appropriate genus to
accommodate these fungi was Ramichloridium. Because
Matsushima's isolate was not available for comparison with the case
isolates and conidia from the brain abscess isolates were smaller than
those for R. obovoideum (4.7 to 9.0 by 2.7 to 4.0 µm
versus 8.8 to 12 by 3.8 to 5 µm), the new name R. mackenziei was proposed in honor of D. W. R. Mackenzie. Our case isolate also had conidial dimensions smaller than
those originally described. Until further isolates are reported for
comparison and current and future isolates are evaluated at the
molecular level, it is difficult to ascertain whether the size of the
conidia is a stable characteristic, a view held by Campbell and
Al-Hedaithy (7), or whether this variability in conidial
dimensions is within the limits for the species (8, 29).
Other dematiaceous hyphomycetes with potential or genuine cerebral
pathogenicity include
C. bantiana (also named
Xylohypha bantiana,
Cladosporium bantianum,
Cladosporium trichoides,
Cladosporium trichoides
var.
chlamydosporum, and
Xylohypha emmonsii),
E. (
Wangiella)
dermatitidis, and
O. gallopavum (
Dactylaria gallopava and
Dactylaria constricta var.
gallopava). The darkly
pigmented ascomycete
C. atrobrunneum is an additional
taxon causing cerebral phaeohyphomycosis.
Characteristics of these five
dematiaceous neurotropic taxa, including
their in vitro
susceptibility data, are outlined in Table
2.
A closely related species,
Chaetomium strumarium, although not
dematiaceous, is also an
agent of brain abscesses (
1). Additional
organisms
which have been reported to invade the CNS include the
graminicolous
(living on grass) species
B. spicifera (
5,
24,
53),
B. hawaiiensis (
31,
41), and
C. pallescens (
16,
26).
R. atrovirens was
also incriminated in CNS involvement in a human
immunodeficiency
virus-positive male drug abuser (
10).
Nonneurotropic dematiaceous fungi sharing macroscopic and
microscopic morphologies similar to those of
R. obovoideum include
R. schulzeri,
R. aquaspersa, and
V. botryosa.
R. schulzeri, which
was reported in a case of "golden tongue" in
a leukemic patient,
is also sometimes seen from respiratory isolates.
It more closely
matches the original description of the genus
Ramichloridium in
that the conidiophores are markedly
differentiated from the vegetative
hyphae, there are numerous conidia
per fertile axis (Fig.
6),
and a distinct
yellow diffusable pigment is usually present.
R. aquaspersa, an agent of human chromoblastomycosis, bears closely
packed hyaline-to-subhyaline and ellipsoid conidia on crowded
denticles.
V. botryosa, an agent of subcutaneous
phaeohyphomycosis
in China, produces predominately two-celled, crowded
conidia on
a sympodially proliferating fertile axis.
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FIG. 6.
R. schulzeri with dark conidiophores and
numerous conidia per fertile axis. Magnification by Nomarski optics,
×920.
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The numbers and types of opportunistic dematiaceous fungi continue to
escalate. While most have occurred in immunocompromised
hosts, patients
without obvious detectable immunosuppression may
also be at risk for
disseminated disease.
R. obovoideum (
R. mackenziei)
should be considered as a possible etiologic agent in
cerebral
phaeohyphomycosis, particularly in patients indigenous to
Middle
Eastern countries. It is also prudent for laboratory workers
studying
this organism to bear in mind its likely neurotropic nature.
Because
of its potential respiratory acquisition and until the route of
infection is clearly elucidated, all studies with this mould,
as well
as with all other filamentous fungi, should be accomplished
with a
biological safety hood.
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FOOTNOTES |
*
Corresponding author. Mailing address: Fungus Testing
Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78284-7750. Phone: (210) 567-4131. Fax: (210) 567-4076. E-mail:
suttond{at}uthscsa.edu.
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Copyright © 1998, American Society for Microbiology. All rights reserved.
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Abstract
Introduction
