Oral histoplasmosis associated with hiv infection: a comparative study
J Oral Pathol Med (2004) 33: 445–50ª Blackwell Munksgaard 2004 Æ
All rights reserved
Oral histoplasmosis associated with HIV infection:a comparative study
S. L. Herna´ndez1, S. A. Lo´pez de Blanc1,2, R. H. Sambuelli3,4, H. Roland3, C. Cornelli3, V. Lattanzi1,M. A. Carnelli4
1Clinical Stomatology B, School of Dentistry, National University of Co´rdoba, Co´rdoba; 2Department of Oral Pathology, HeadProfessor of Clinical Stomatology B, Faculty of Dentistry, National University of Co´rdoba, Co´rdoba; 3Rawson Hospital Co´rdoba,Co´rdoba; 4Department of Pathology, Catholic University of Co´rdoba, Co´rdoba, Argentina
OBJECTIVE: Histoplasmosis is a granulomatous fungal
river valleys of the world between latitudes 45° north
disease caused by Histoplasma capsulatum. The objective
and 30° south of the equator (1, 4, 6–15). In Argentina,
of the present paper was to describe the prevalence
the endemic region is around the central, east and
of oral histoplasmosis (OH) in two services from an
endemic area in Argentina between 1991 and 2002 and to
Clinically, histoplasmosis has been classiﬁed as: (i) a
compare the clinicopathological profile of OH between
primary acute pulmonary form, (ii) a chronic pulmonary
HIV-positive and HIV-negative patients.
and (iii) a disseminated form (DH) occurring in infants,
METHODS: About 733 HIV+ (group A) and 14 260
elderly or in immunocompromised patients (6, 19–23).
patients (group B) were examined. Clinical diagnosis was
In 1985, the Centre for Disease Control added DH to
confirmed by cytology, biopsy or culture.
the spectrum of infections that characterize the acquired
RESULTS: About 21 (3%) and 10 (0.07%) cases of OH
immunodeﬁciency syndrome (AIDS). The main reason
were diagnosed in group A and B respectively. Most
for the delay in recognizing histoplasmosis as an
patients were male. A total of 90% of patients in group A
opportunistic infection in those patients was that early
were <45 years old whereas 70% of group B were more
AIDS cases appeared ﬁrst in non-endemic areas. With
than 45 years old. Palate, gingiva and oropharynx were
spread of the disease to endemic areas, it has emerged as
the most frequent locations. The importance of including
an important opportunistic infection in patients with
histoplasmosis in the differential diagnosis of ulcerated
AIDS (8, 9, 24, 25). About 30–66% of patients with DH
have oral lesions, frequently presenting as the initial
sign. Generally lesions of histoplasmosis in the oral
cavity, are the local manifestation of pulmonary ordisseminated disease (16, 26) but rarely they may be the
Keywords: histoplasmosis; human immunodeficiency virus; oral
primary or even the only manifestation of the disease
(3, 4, 8, 10, 16, 17, 27–29). The diagnosis is usually basedon clinical signs and symptoms, organ function tests andfungal demonstration or culture from a lesion orsecretion. Serological testing may help together with
other suggestive but non-diagnostic clinical criteria (4–6,
Histoplasmosis is a granulomatous fungal disease of
11, 17). Recently, molecular typing of H. capsulatum has
worldwide distribution caused by Histoplasma capsula-
been shown to be useful in distinguishing relapse from
tum. The infecting agents are airborne spores from the
reinfection, and in deﬁning the likely source of the
mycelial form. It is usually found in warm, humid
infection (21, 30, 31). Furthermore, molecular typing of
environments that contain bird and bat excreta (1–7).
H. capsulatum by the random ampliﬁed polymorphic
The most endemic areas for H. capsulatum are certain
method, is able to discriminate among clinical iso-lates, making it a useful tool for epidemiological investi-
Dra Silvia Lo´pez de Blanc, Ca´tedra de Clı´nica
Estomatolo´gica I y II B, Facultad de Odontologı´a, Pabello´n Argen-tina, Ciudad Universitaria, Agencia 4, (5016) Co´rdoba, Argentina.
Tel: 0351-4659564, Fax: 0351-4334179-78, E-mail: firstname.lastname@example.org.
Historically, amphotericin B has been the drug of choice
edu.ar, email@example.comAccepted for publication March 11, 2004
for systemic histoplasmosis (1–3, 8, 12, 16, 17, 32–37).
The options have broadened considerably since the
CD4 count in HIV+ patients was 60/mm3 and ranged
introduction of the azole compounds, ketoconazole and
Oral lesions had similar clinical presentation in both
The aim of the present paper is to describe the
groups, described as painful granulomatous ulceration.
prevalence of OH in two services from an endemic area
The lesions began as erythematous, painful red patches
in Argentina and to compare the clinicopathological
(see Fig. 1) that latter became elevated, granulomatous
proﬁle of histoplasmosis oral lesions of HIV-infected
and ulcerated as shown in Fig. 2. The ulcerations were
(HIV+) and HIV-negative (HIV)) patients.
covered by yellowish pseudomembranes diﬃcult toremove and tender to palpation. Most of the patientsin both groups, had more than two lesions. The most
frequent locations were hard and soft palate, gingiva
In this retrospective study, the clinical records made by
and oropharynx, followed by tongue. Gingival lesions
us in HIV+ patients of Rawson Hospital: group A, and
were associated with bone loss. Presence of histoplas-
in those attended in Clinical Stomatology B (a referral
mosis was diagnosed by cytology, culture, biopsy or
clinic for oral soft-tissue lesions): group B, between
December 1991 and December 2002 were revised inorder to analyse and compare the prevalence of OH in
both groups. Group A included 733 patients and group
Yeast forms were quite easily visualized in cytological
B 14 260. Written consent was obtained from each
smears or biopsies. The smears revealed in addition to
patient before the study; oral examinations and the
squamous cells of the oral mucosa, several erythrocytes,
diagnosis at both centres were made by the same trained
neutrophils and macrophages-containing intracellular
professionals and supervised by the head professor. All
spherical to ovoid bodies each surrounded by a small
the patients with OH were tested for HIV infection and
light halo (Fig. 3). Biopsy specimens showed a normal
the HIV-positive excluded of group B. When an
maturing, thinly stretched and ulcerated stratiﬁed squ-
ulcerated granulomatous lesion suggesting OH was
amous epithelium. The lamina propia showed focal
found, the diagnosis was based on the demonstration
accumulations of mononuclear macrophages stuﬀed
of the microorganism in biopsies, cytological smears or
with 2–5 micron fungal yeasts and some isolated
culture (4–7, 11, 16). Biopsies were stained with haem-
organisms that stained highly positive with PAS and
atoxylin and eosin and with periodic acid-Schiﬀ (PAS)
1 GSM. Yeast forms were seen intracellularly within the
stain reaction; in some cases the Grocott silver methen-
histiocytes, and as described in the literature, they had a
amine (GSM) procedure was used. Cytological smears
thin wall instead of a true capsule (39). The ulcerated
were stained with May Gru¨ndwald Giemsa (MGG) and
surface was coated with ﬁbrin and the area beneath the
with Papanicolaou stain (EA36-Hematoxylin). Addi-
ulcer showed a moderate acute inﬂammatory inﬁltrate.
tional conﬁrmation was obtained by isolation and
Several small microorganisms, with frequent transepi-
identiﬁcation of the organism from tissue or secretion
thelial migration were found in group A, whereas in
cultures. The tissue was added to the following media:
group B they were scarce but more voluminous. On the
Sabouraud dextrose agar + chloramphenicol, ampicil-
contrary, conspicuous granulomas with giant cells were
lin and gentamicin. The tubes were incubated at 28°C
observed in HIV) patients (Fig. 4), whereas in group A
to observe the mycelial and at 35°C to observe the
they were exceptional. Vasculitis phenomena were
levaduriform or infecting form. Positive colonies were
occasionally observed. Cultures were positive in seven
then transferred to blood agar plates and incubated at
35°C, eventually resulting in conversion to the yeast
The OH was marker disease in 10 HIV+ patients
form. The diagnosis was conﬁrmed by the dimorphism
(48%). The treatment was dependant on the immuno-
logical condition of the patient, and on the availabilityof drugs in our public hospital. In 14 cases of the groupA the treatment begun with amphotericin B, and when
the infection was controlled, an azole antifungal was
In group A (HIV+ patients), 21 (3%) had OH, while
used; in six cases it was controlled only with itracon-
in group B (HIV)) only 10 (0.07%) did. The analysed
azole. This was the drug of choice in group B. The
data on age, gender, general condition, other involve-
evolution was good in all patients but three of group A
ment and diagnosis of these patients are shown in
relapsed some months later, only two died after therapy
Table 1. The age ranged from 23 to 77 years. Nineteen
but histoplasmosis was not the cause of death.
patients (90%) in group A, were <45 years oldwhereas seven (70%) in group B were more than
45 years old, indicating a positive correlation betweenage and HIV infection in patients with OH (P ¼
Most investigators believe that human infection occurs
Fisher’s exact test). Most of the patients were male,
via inhalation of aleuriospores in dust (5, 6, 15). Ritter
81% in group A and 90% in group B. Weight loss
(40) and Gordon et al. (41), however, suggest that at
followed by persistent cough and dysphagia, were the
least in some instances the spores gain entry to the
most frequent symptoms in both groups; in addition,
gastrointestinal tract from contaminated drinking water.
67% of the HIV+ patients had fever. The average of
On the contrary, some investigators claim that primary
Oral histoplasmosis in HIV+ patientsHerna´ndez et al.
Clinical features of an HIV+ patient. Red patch involved
Cytological smear from an HIV+ patient, showing several
the marginal and attached gingiva of the anterior area; ulcerated
macrophages containing intracellular spherical to ovoid bodies, each
lesions of the premolar area are also present.
surrounded by a small light halo (papanicolaou stain, originalmagniﬁcation ·100).
Clinical features of an HIV patient showing an elevated
granulomatous lesion in hard palate and right maxillary gingiva.
Biopsy specimen showing a granulomatous suppurated
lesion from an HIV patient and the Histoplasma capsulatum within a
OH is possible and may occur from direct inoculation of
giant cell (haematoxylin and eosin stain, original magniﬁcation ·60).
the fungus into the mucosa (4, 5, 24). The possibility ofhuman-to-human transmission between sexual partnersis still an intriguing question (42). In the cases analysed
among females was found in HIV+ patients, a
in this paper OH lesions were found 43 times more
tendency also observed by Casariego et al. (45). Most
frequently in HIV+ vs. HIV) patients; in addition all
patients had a favourable response to the therapy; only
the HIV) patients lived on a farm or worked in contact
two died after therapy but histoplasmosis was not the
with bird and bat excreta, whereas it was very diﬃcult
to establish the source of contamination in HIV+
This report shows the importance of including OH in
patients. Clinical presentation and location of the oral
the diﬀerential diagnosis of ulcerated lesions in immu-
lesions as well as the average of CD4 count (60/mm3)
nocompromised patients. Early recognition and prompt
were similar to those reported by other authors (11,
management of these infections are of paramount
32). Although histoplasmosis is a disease that tradi-
importance in maintaining the health and prolonging
tionally aﬀects old people (12, 16), since the appearance
of AIDS its prevalence has increased in younger peopleas in the present study (32, 43, 44). From these resultsit can be inferred that if histoplasmosis is diagnosed
in a young patient, then a search for current HIV
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Soft X-ray Emission and Lithium Production in Cen X-4 duringShin-ichiro Fujimoto,1 Ryuichi Matsuba,2 and Kenzo Arai,31 Department of Electronic Control, Kumamoto National College of Technology,2659-2 Suya, Koshi, Kumamoto 861-1102, Japan2 Institute for e-Learning Development, Kumamoto University, Kumamoto 860-8555, Japan3 Department of Physics, Kumamoto University, Kumamoto 860-8555, Japan E
CLADES, CAPGRAS, AND PERCEPTUAL KINDS Jack Lyons University of Arkansas Perceptual states represent the world as being certain ways, as having certain properties. Which ways and properties are these? When I hold out my hand and look at it, it seems that Ihave a visual experience of a hand. One traditional view has held that my perceptual state is notof a hand but merely of an array of colo