73
Dematiaceous Fungi Are an Increasing Cause of Human Disease
Susan Norton Rossmann, Patricia L. Cernoch,
and James R. Davis
From The Methodist Hospital and Baylor College of Medicine,
Houston, Texas
The dematiaceous fungi appear to be an increasing cause of human disease. At The Methodist
Hospital, in Houston, Texas, five cases of serious disease caused by these fungi occurred between
1987 and 1992. Cerebral abscesses with Xylohypha bantiana followed treatment for lymphoma. An
infection of the lower extremity with Exophiala jeanselmeivar. castellanii followed cardiac surgery.
Peritoneal growth of Alternaria tenuissima was a complication of peritoneal dialysis. Cerebral
abscesses with Dactylaria gallopava occurred in a liver transplantation patient. A traumatic ankle
wound contaminated with dirt led to an infection with Phialophora repens. All patients except the
last were immunocompromised at the time of the infection; diabetics and patients on steroids may
be at particular risk.
The dematiaceous fungi are a heterogeneous group of organisms unified by their production of melanin pigments. They
are widely found in nature but are not common human pathogens. At The Methodist Hospital in Houston, Texas, a 1,500bed primary and tertiary care hospital and teaching facility of
Baylor College of Medicine, five cases of serious disease
caused by a variety of dematiaceous fungi occurred between
1987 and 1992. A variety of sites and organisms were involved,
and no common mechanism is postulated. Most of the patients
were immunocompromised; many had disturbances of carbohydrate metabolism due to diabetes or because of treatment
with steroids. These cases are reported here to draw attention
to this group of organisms as an apparently increasing cause
of disease and also to unusual presentations of disease with
Exophiala jeanselmei var. castellanii and Dactylaria gallopava.
The dematiaceous fungi are usually defined as those that
have melanin or melanin-like pigment in the wall ofthe hyphae
and/or spores [1]. Invasive disease caused by these organisms
is called phaeohyphomycosis [2], from the Greek "phaeo,"
meaning dark; it is largely diseases of this class that we will
be describing here. More superficial, subcutaneous infection is
called chromoblastomycosis and is characterized histologically
by pseudoepitheliomatous hyperplasia and the presence of pigmented sclerotic bodies [3-6]. Mycetoma, a tumorous growth
of the skin, may also be caused by dematiaceous or hyaline
fungi (eumycotic mycetoma) as well as by actinomycetes (actinomycotic mycetoma) [7 -9]. An excellent review of the dematiaceous fungi has recently been published [10].
Received 1 May 1995; revised 7 August 1995.
This work was presented in part as abstract no. F-87 at the 92nd General
Meeting of the American Society for Microbiology in May 1992 (New Orleans).
Reprints or correspondence: Dr. Susan N. Rossmann, Texas Children's Hospital, Pathology Department, MCI-2261, 6621 Fannin Street, Houston, Texas
77030.
Clinical Infectious Diseases 1996;22:73-80
© 1996 by The University of Chicago. All rights reserved.
1058--4838/96/2201-0013$02.00
The dematiaceous fungi are also increasingly recognized in
association with a severe form of sinusitis characterized by a
unique histologic picture. Such sinusitis was initially attributed
to Aspergillus species and was designated "allergic aspergillus
sinusitis" [11, 12]; however, in fact, Aspergillus species are
only occasionally found in such cases, and the dematiaceous
fungi, especially those of the genera Curvularia, Bipolaris, and
Exserohilum, are quite commonly seen [13, 14]. The pathogenetic mechanism in such cases is not well defined, but the
condition appears to represent a tissue response ("allergic"
response) to the presence of fungi. The disease clinically may
act in an invasive fashion, eroding the sinus and extending into
the brain. However, the hyphal elements usually are seen only
in a characteristic exudate and do not, in the strict pathological
sense, invade native tissues. A similar "allergic" response to
dematiaceous fungi has been reported to cause pulmonary disease [15]. We have noted an increasing number of cases of
sinusitis associated with dematiaceous fungi; these are not included in this report.
The dematiaceous fungi that have been reported to cause
phaeohyphomycosis are numerous. Fifty-nine species of 28
genera and three classes are reported in a recent text [1]. In
addition to the confusion caused by this wide variety of organisms, some of which are associated with but a single case of
disease, the taxonomy and nomenclature of this field undergo
constant revision and are controversial (see, for example, [16,
17]). Thus, a single organism may be identified by a variety
of names in the recent and historical literature, a circumstance
that contributes to confusion for clinicians and for all but the
most dedicated mycologists. This review does not attempt to
deal definitively with the contentious and difficult questions of
mycological classification and nomenclature that have marked
the study of dematiaceous fungi, but alternative names or appropriate synonyms will be given in each case.
Methods
The materials were received at the microbiology laboratory
and processed routinely for fungal cultures; all isolates were
identified by the Fungus Testing Laboratory of the University
cm
Rossmann, Cemoch, and Davis
74
1996;22 (January)
Table 1. Characteristics of patients with infections due to dematiaceous fungi at The Methodist Hospital in Houston (1987 ~ 1992).
Age (y)/
sex of patient
Site
77/F
Brain, CSF
Xylohypha bantiana
2
69IM
Leg
3
331M
Peritoneum
4
59IM
Brain
Exophiala jeanselmei
var. castellanii
Alternaria
tenuissima
Dactylaria gallopava
5
4lIM
Ankle
Phialophora repens
Case no.
Organism
Medical history
Treatment (total dose)
Outcome
Previous Hodgkin's disease, nonHodgkin's lymphoma
Vascular compromise following
coronary artery bypass, diabetes
End-stage renal disease, peritoneal
dialysis
Liver transplantation
AmB (~l g),
flucytosine
Amputation
Died; fungus in brain
at autopsy
Died; no autopsy
Lysis of adhesions;
AmB (2.5 g)
ArnB (2.5 g)
Well at discharge
Forklift injury with dirt
contamination
Debridement; AmB (750 mg);
ketoconazole
Died; no fungus in
brain at autopsy
Healed
NOTE. AmB == amphotericin B.
of Texas Health Science Center at San Antonio (Dr. Michael
Rinaldi, Director). Our nomenclature follows their reports,
modified slightly to meet current usage. The cases are listed
in table 1; more detailed discussion follows.
Case Reports
Case 1. A 70-year-old woman was treated for large-cell
lymphoma in 1982 and received chemotherapy and radiation.
In 1987 she had a cutaneous infection with Blastomyces dermatitidis, which was treated with ketoconazole. Persisting enlarged lymph nodes were biopsied, and Hodgkin's disease, of
unknown type and stage, was diagnosed. She received chemotherapy. The next year a slow decline in mental status began
with confusion and lethargy. After several months a CT scan
was performed, which showed a cerebellar mass. A biopsy
was performed elsewhere, yielding purulent material, and the
organisms cultured from this were reported to be Cladosporium
trichoides. The mass was totally excised, and she was treated
with ~ 1 g of amphotericin B. Her condition gradually improved over several months, but her declining mental status
led to a lumbar puncture, and cultures of this fluid yielded the
same organism. She was treated with flucytosine of unknown
dose and duration, but progressive deterioration in level of
consciousness and high spiking fevers were noted.
She was transferred to our hospital. A CT scan showed
dilatation of the right lateral ventricle with an enhancing area
in the region of the foramen of Monro on the right side. An
Ommaya reservoir was placed in the right frontal region by
ventriculostomy. At this time fungal cultures of a liver specimen, peritoneal fluid, bone marrow, and CSF were negative.
No further antifungal therapy was given. Three weeks later
the patient was found without pulse or respiration and was
pronounced dead. At autopsy the brain had multiple fungal
abscesses and hemorrhagic necrosis, involving the thalamus,
basal ganglia, fornix, corpus callosum, pons, cerebellum, and
cervical cord (figures 1 and 2). Autopsy cultures of brain specimens yielded Xylohypha bantiana. No evidence was found of
lung involvement or other dissemination.
This case graphically demonstrates the clinical confusion
that can be caused by nomenclatural changes in mycology.
Presumably, the same infection was reported from different
institutions as C. trichoides and X bantiana. The organism has
been variously called C. trichoides, Cladosporium bantianum,
and Torula bantiana and most recently has been classified
as X bantiana, with C. bantianum as a synonym [18]. This
reclassification has been the subject of dispute [1, 19], and
cases may currently be reported under either name.
Under its various names, X bantiana is known to be a common source of cerebral phaeohyphomycosis, accounting for
~50% of cases in several series [1]. These infections occur
in apparently immunocompetent individuals, especially young
males [20-23], as well as in those immunocompromised by
steroids [24], cancer [25], transplantation [26], or decreased
immunoglobulin levels [27]. Most patients present with mental
status changes, and the frontal location is most common [23].
Extension from paranasal sinuses has been reported [28].
Chronic meningitis, without cerebral invasion, has also been
demonstrated [29]. Most cases of infection with X bantiana
cause CNS disease [23], although a few pulmonary cases have
been reported [30].
Skin involvement has been proposed to be a source of cerebral disease, but this has not been demonstrated [31]. Exposure
to soil may be a risk factor [23]. The multiplicity of abscesses
in many cases argues for a hematogenous spread; a portal of
entry, presumably pulmonary, is rarely documented. One case
involving a 61-year-old man with lymphopenia and an absence
of T-helper cells has been reported [32]. This history is clearly
suggestive of AIDS, but this and other reports were published
well before the clinical occurrence of AIDS became common,
and no HIV status is reported for most of the patients. The
outcome of cerebral xylohypha infection is very poor with
antifungal therapy alone, and neurosurgical debridement appears essential for any hope of cure. Even with aggressive
surgical and medical treatment, mortality probably exceeds
50% [23].
Case 2. A 69-year-old man with unstable angina was admitted to our hospital. He had a 5-year history of adult-onset
Figure 1. Autopsy of the brain of patient 1 revealed a mass of faintly pigmented hyphal elements
of Xylohypha bantiana (right) occupying the ventricle; ventricular lining cells are seen to the left (stain,
hematoxylin and eosin; original magnification,
X 100).
Figure 2. Autopsy examination of the brain of patient I revealed
the hyphae of Xylohypha bantiana, well seen in this Fontana-Masson
preparation, which stains the melanin (original magnification, X 100).
Figure 4. Variably pigmented elements of Alternaria tenuissima
assume unusual forms in the peritoneal cavity of patient 3 (stain,
hematoxylin and eosin; original magnification, X 100).
Figure 3. The small yeast forms and pseudohyphae of Candida
albicans are on the surface (right) of the leg of patient 2, while the
pigmented hyphae of Exophiala jeanselmei var. castellanii are more
invasive, found deeper in the necrotic tissues (left) (stain, hematoxylin
and eosin; original magnification, X 10).
Figure 5. An abscess cavity in the brain of patient 4 is lined by the
hyphal elements of Dactylaria gallopava, stained black by GrocottGomori methenamine-silver nitrate stain (original magnification,
X 10).
76
Rossmann, Cernoch, and Davis
diabetes mellitus. For three years he had had peripheral vascular disease, with claudication of the calf. Doppler evaluation
revealed left aorto-iliac artery obstructive disease and mild
right tibial artery obstructive disease. A cardiac angiogram
demonstrated severe coronary artery disease. The patient underwent coronary artery bypass grafting with saphenous leg
veins and the left internal mammary artery. On postoperative
day 6 the patient had a right iliac artery occlusion, which was
treated with a right-to-left femoral-femoral bypass. A right
common femoral thrombus later developed, and a thrombectomy was performed.
Following thrombolytic therapy, a hemopericardium developed, which required a second sternotomy. Glucose levels and
renal function were difficult to control, and peritoneal dialysis
was begun. Adult respiratory distress syndrome developed, and
inotropic support was required. In the right lower extremity,
cyanosis and ischemia developed. Fasciotomy was performed
and local treatment was administered, but dry gangrene eventually required an above-the-knee amputation, 26 days after the
original cardiac surgery. Cultures of specimens from the leg
yielded Exophiala castellanii (now regarded as a variant of
E. jeanselmei [33]) and Candida albicans. No other organisms
were isolated. The patient's condition continued to deteriorate,
and he died 4 days after the amputation. No antifungal therapy
was given. No autopsy was performed.
Pathological examination of the amputated limb showed the
skin to be covered extensively with a mixed infection due to
Exophiala and Candida species. The morphological appearance
was quite striking (figure 3), with invasive pigmented Exophiala hyphae covered with more superficial candidal forms.
The patient's right leg was compromised locally by a number
of factors: peripheral vascular disease, postoperative thrombus
formation, and the high levels of peripheral vasoconstriction
necessary to support systemic blood pressure. Thus, the limb
was ischemic. In addition, the patient had a number of specific
systemic problems that may have compromised immune function: he had long-standing diabetes, with very poor glucose
control during this episode; he had had massive blood transfusions, known to be immunosuppressive [34]; and he had (terminally) poor renal function, also immunosuppressive. Multiple
blood cultures were negative. The sputum, as well as the leg,
yielded C. albicans, but no specific features of fungal pneumonia were seen.
E. jeanselmei var. castellanii was at one time considered a
new species, E. castellanii [35]. It is commonly regarded as a
variant of E. jeanselmei [33]. To our knowledge, no other
cases of human disease with this variant have been reported.
E. jeanselmei is a relatively common cause of subcutaneous
and skin infections [36]. For example, its presence in a hand
infection in a renal transplantation patient receiving steroids
has been reported. This lesion healed completely with administration offlucytosine [37]. In a boat-builder who was receiving
steroid therapy for a rheumatic condition, knee and elbow lesions developed that yielded both Phialophora richardsiae and
E. jeanselmei. In this case, the former organism was regarded
em
1996;22 (January)
as the primary pathogen and the latter as a copathogen or
contaminant, but no basis for this opinion was given [38]. The
histologic findings in both of these cases were similar to ours:
scattered, pigmented hyphae and spores within a dense inflammatory infiltrate. The growth in our case was more luxuriant, presumably because of poor circulation.
Endocarditis and arthritis have also been reported, in an
unusual case following injection of steroids into the knee [39].
In patients with AIDS, E. jeanselmei may rarely cause esophagitis that is difficult to distinguish from candidiasis [40]. Wangiella dermatitidis, a closely related species also called Exophiala dermatitidis [1], usually causes more systemic and
neurotropic infections [41]. W. dermatitidis is also increasingly
recognized in patients with cystic fibrosis [42,43], and in some
unusual cases it may cause lung disease in those without cystic
fibrosis [44]. The pathogenicity of the organism in patients
with cystic fibrosis is controversial; some investigators believe
that its presence represents colonization rather than disease.
Exophiala mansonii has also been reported to cause synovitis
in a renal transplant recipient [45] and skin disease following
possible trauma in a patient receiving chemotherapy [46]. Skin
lesions due to Exophiala pisciphila [47] as well as Exophiala
spinifera [4] have been reported. The morphological similarity
of E. spinifera and E. jeanselmei has led to the development
of an exoantigen assay [48] that may be useful in some cases.
Case 3. A 34-year-old man with renal failure who was
being treated with continuous ambulatory peritoneal dialysis
(CAPD) had chronic peritonitis and small-bowel obstruction.
Culture specimens from a surgical exploration of the peritoneum yielded Alternaria tenuissima. Histology of the surgical
specimen revealed numerous large pigmented hyphae in the
peritoneal fluid and fibrinous exudate (figure 4). He received
910 mg of amphotericin B while hospitalized and was well at
discharge. Administration of a total of 2.5 g of amphotericin
B was planned.
Individuals being treated with CAPD are at increased risk
of fungal infections in several ways. The occurrence of uremia
or renal failure itself causes a state of immunosuppression,
as leukocyte function is impaired. In addition, the indwelling
catheter used for peritoneal dialysis provides an easy port of
entry in these patients. Renal transplant recipients, of course,
are immunosuppressed and thus-like other transplant recipients-are subject to fungal infections [45, 49, 50].
As many as 60% of patients undergoing CAPD have peritonitis in the first year [51]. In most series, three-fourths of the
organisms are gram-positive, approximately one-fourth are
gram-negative, and less than 5% are fungi [51]. Among these
fungi, Candida is the most common organism, and both Candida parapsilosis and C. albicans are frequently reported [52].
Other, more unusual yeasts and molds have also been reported,
including Trichosporon beigelii [53] and the dematiaceous
Lecythophora mutabilis (previously called Phialophora mutabilis) [54] and Curvularia species [53, 55, 56]. Alternaria species have been reported in two previous cases [57, 58]. Fungal
peritonitis may follow antibiotic therapy, and it is unclear if
em 1996;22 (January)
Dematiaceous Fungi
this sequence simply reflects the common co-occurrence of
bacterial and fungal infections or if antibiotic therapy is an
independent risk factor for fungal infections [52]. Diabetics
undergoing CAPD may be at particularly elevated risk offungal
peritonitis [52].
Case 4. A 59-year-old man presented with mental status
changes. Two years previously he had received a liver transplant for cirrhosis of unknown etiology, and at the time of
presentation there was evidence of severe rejection despite the
administration of steroids and other immunosuppressive therapy. Two months before this presentation, an episode ofbacteremia and pulmonary infection with Nocardia asteroides had
occurred; it had been treated and apparently resolved. At the
current presentation, he was lethargic and confused, with right
hemiparesis. A CT scan revealed multiple cerebral lesions, and
a biopsy of one of the brain lesions was performed. Histologic
examination showed extensive granulomatous inflammation
and cavity formation (figure 5), and cultures yielded D. gallopava. Other specimens, from the lung, yielded N. asteroides.
The patient was treated with 2.5 g of amphotericin B but succumbed to liver failure in ~ 2 months. At autopsy, no residual
fungal disease was present in the brain, as determined by culture and histology. Only a limited autopsy was permitted, and
the lungs were not examined.
The taxonomy and nomenclature of the Dactylaria genus
and the closely related Scolecobasidium genus have been controversial. Mycologists de Hoog and van Arx combined
D. gallopava, Scolecobasidium humicola, and Scolecobasidium
tshawytschae to make a new genus, Ochroconis, but this classification has not been entirely accepted [1, 59]. Salkin and Dixon
proposed, on morphological grounds, that D. gallopava be regarded as Dactylaria constricta var. gallopava, while Scolecobasidium constrictum be regarded as Dactylaria constricta
var. constricta [60]. This assignment has been contested by
others, who argue that the antigenic and physiological differences between the organisms are sufficient to retain two species: D. gallopava and S. constrictum [61].
Two cases of cerebral involvement with D. gallopava, both
in immunocompromised hosts, have been previously reported.
One involved a patient from North Carolina with large-cell
lymphoma, in whom a single right frontal lesion developed [62].
The patient had previously had N. asteroides infection, which
had presumably been cured by the time of the dactylaria infection. In this report, the organism is called Ochroconis gallopavum. The second case involved a diabetic patient with T-cell
chronic lymphocytic leukemia, who had widely disseminated
D. gallopava infection [63]. Both patients died. Subcutaneous
D. gallopava (reported as 0. gallopavum) infection has also
been reported to occur in a patient with myeloid leukemia, in
Japan [64]. S. constrictum (called Ochroconis constrictum in the
publication) was also indirectly reported as a cause of a brain
abscess in a diabetic patient from Louisiana [64]. All of these
patients were immunocompromised, and most had some disturbance ofcarbohydrate metabolism, via either primary diabetes or
steroid treatment. A propensity for infection in the southeastern
77
United States has been noted, but this organism has also been
isolated from thermal pools in Yellowstone National Park and
thermal effluents of nuclear reactors [64, 65].
It is interesting that a number of other cases of cerebral
phaeohyphomycosis with various species have been reported
in association with N. asteroides [20, 27, 32, 62]. While underlying immunosuppression may be suspected in all these patients, the association seems stronger than might be expected
by chance. Presumably the patients, already compromised in
some way, acquired a nocardia infection (pulmonary or disseminated) that may have predisposed them to the acquisition of
a fungal infection, possibly acquired initially through a pulmonary source. Such a pulmonary origin is the frequently presumed but rarely documented portal of entry for the dernatiaceous fungi when they are found in other areas of the body.
The previous occurrence of nocardia infection may delay diagnosis of the fungal infection, as the patient may receive treatment for presumed recurrence of nocardia infection.
Case 5. A 41-year-old man sustained a forklift injury to
his left ankle. The wound was contaminated by dirt. There was
no evidence that he was immunocompromised, and he was
HIV-negative. Following the injury, he had a bone chip surgically removed. The ankle gradually developed fluctuant and
draining abscesses. Cultures 3 months after the accident yielded
only rare Bacillus species, which were regarded as contaminants. Fungal cultures were not performed at this time. He was
treated with minocycline and his wounds healed well.
Five months post-injury a purulent discharge was noted
again, and cultures of specimens from the surgical debridement
yielded methicillin-resistant Staphylococcus aureus but were
negative for other bacteria, fungi, or acid-fast bacilli. He was
treated with a 6-week course of vancomycin. The wound continued to drain and form abscesses, and osteomyelitis developed. Cultures of specimens from surgical debridement, now
10 months after the injury, yielded Phialaphora repens, Sporothrix schenckii. and no bacteria. Histology revealed rare pigmented sclerotic bodies in a dense inflammatory infiltrate. The
wound was surgically debrided and the patient received a total
of 750 mg of amphotericin B before this drug was withdrawn
because of renal toxicity. The patient healed well. At this time
the patient's therapy was switched to oral ketoconazole (200
mg b.i.d.), which was to be administered for several months.
Both S. schenckii and P. repens were isolated from the last
debridement specimen. However, there was no histologic evidence of sporothrix infection, while the sclerotic bodies seen
with a dematiaceous organism such as Phialophora were demonstrated. Moreover, the lymphatic involvement characteristic
of sporothrix infection was not seen. The clinical and histologic
evidence thus support the pathogenicity of P. repens.
P. repens is a cause of bluish staining in timber and is
commonly found in nature. Other species of Phialophora (richardsiae, parasitica, verrucosa, and mutabilisi are more commonly reported as the cause of human disease, including phaeohyphomycosis, keratitis, and disseminated disease. P. repens
was reported in 1975 as a cause of a subcutaneous granuloma-
78
Rossmann, Cernoch, and Davis
tous scalp nodule in an African patient with lepromatous leprosy who was being treated with corticosteroids [66]. In a
second case, P. repens was cultured from the dorsum of the
hand of an otherwise healthy Japanese man [67]. No specific
trauma was reported or could be recalled in either previously
published case.
In our case, fungal cultures were not performed when posttraumatic infection was first noted, and they were negative
when first done 5 months later. Fungal organisms were not
identified in several surgical specimens, although they were not
suspected and were not specifically sought. Moreover, because
tissue response is nonspecific, the sensitivity of histopathology
is poor. The history of initial trauma, the indolent course, and
the histology suggest that a Phialophora species caused disease
from the beginning, and the negative cultures at 3 months may
have been due to the very small number of fungal organisms
present in the tissue, embedded in a dense fibrous matrix. It is
less likely that the wound may have been secondarily infected
with this fungus.
Discussion
In our series we have two infections of the CNS, one peritoneal infection, and two infections of the lower extremities. One
extremity infection appeared to be a classic example of dirt
contamination of a penetrating wound; most of the other cases
involved invasive disease. All ofthese cases ofinvasive disease
occurred in patients who had some source of immune compromise, particularly cell-mediated immunity; these conditions
ranged from immunosuppressive therapy for transplant rejection to peritoneal dialysis. Despite the relatively large number
of patients with AIDS seen at our hospital, no cases in this
series involved patients with AIDS, and such cases have not
often been reported by other investigators.
Ofparticular interest is the frequent presence ofa disturbance
in carbohydrate metabolism, due to frank preexisting diabetes
or the use of steroids, both of which are known to disturb
carbohydrate metabolism as well as cell-mediated immunity.
An association of diabetes with other fungal infections, notably
candidal infections and invasive disease with the zygomycetes,
has long been noted, although the mechanism is not entirely
clear (see review in [68]). Many other reports as well have
documented infections with dematiaceous fungi in diabetic patients [36,49,54-57,67,69, 70]. Possible mechanisms include
impaired neutrophil, macrophage, and complement function in
the diabetic [71].
An additional large group ofinfections involves those receiving steroids [24, 30, 37-39, 45, 47, 50, 64, 66, 70, 72-74];
some of these patients had no other known immunosuppressive
conditions. An experimental model has shown a direct effect
of steroids on CNS infections with X bantiana (75]. With
regard to steroids, of course, we must consider the underlying
disease that led to treatment with the drugs, as well as the direct
immunosuppressive role of the steroids themselves; several
mechanisms, including those related to carbohydrate intoler-
cm
1996;22 (January)
ance as well as other factors in cell-mediated immunity, may
be involved. Our report confirms the observation ofother investigators [76] that these fungi are increasingly likely to be the
causes of human disease, and it suggests that diabetic patients
or persons receiving steroids may be particularly susceptible.
The dematiaceous fungi, many of which are common in the
environment, cause disease only rarely, usually in the compromised host. As our patient population consists more and more
of such persons, we must look carefully to diagnose these stillunusual fungal infections.
Acknowledgments
The authors appreciate the clinical information provided by the
physicians caring for these patients, especially Drs. Major Bradshaw, Victor Fainstein, Richard Harris, Tobias Sarno, and Temple
Williams.
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