Sindrome de addison

1. Addison’s disease associated to
paracocidioidomycosis
Claudio Maranhão Pereira
3
Silmara Regina Silva
1
Priscila Spaziane Camargo
1
Andrea Mantesso
2
Rodrigo Calado Nunes Souza
1
1
Dentistry Section, Municipal Healthy Service,
Campinas-SP, Brazil
2
Oral Pathology, São Leopoldo Mandic Dental
Research Institute, Campinas-SP, Brazil
3
Oral Pathology, School of Dentistry of
Piracicaba, UNICAMP, São Paulo, Brazil
Received for publication: September 30, 2003
Accepted: March 2, 2004
Correspondence to:
Claudio Maranhão Pereira
Faculdade de Odontologia de Piracicaba-
UNICAMP
Semiologia e Patologia Oral -Diagnóstico Oral
Av. Limeira, 901 - Areião - Caixa Postal 52 -
CEP: 13414-900 - Piracicaba/SP - Brazil
+ 55 19 3412 5213;
Fax: + 55 19 3412 5218
E-mail: [email protected]
Abstract
Paracoccidioidomycosis is a deep mycosis caused by the
Paracoccidioides brasiliensis and it has been considered the most fre-
quent systemic mycosis in Latin America. Mulberry-like ulcers on the
oral mucous membranes are one of the earliest manifestations of the
disease. Infection may remain subclinical, localized or disseminate oc-
casionally.
Adrenal involvement by granulomatous diseases is the main cause of
this gland insufficiency in Brazil. The aim of this study is to report one
case of oral paracoccidoidomycosis that provided the diagnosis of the
systemic mycosis disease with secondary Addison’s disease. In spite
of not being rare the involvement of the adrenal glands for the P.
brasiliensis, it was not possible to find in the literature another case
with oral clinical and progression features similar to this.
Key Words:
Addison’s disease, paracoccidioidomycosis, adrenal glands.
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2. Introduction
Paracoccidioidomycosis (South America blastomycosis)
is a chronic mycosis disease caused by the dimorphic
fungus Paracoccidioides brasiliensis
1-2
. Geographic
fungal distribution is restricted to Latin America where it
is considered the most prevalent systemic mycosis
3-5
. It
is still relatively unknown in the United States and
Europe
4,6
.
P. brasiliensis may grow in the soil, in water, on plants in
rural areas, and reaches the human host by the inhalation
of airbone propagules
5
. Ninety per cent of cases have
occurred in males patients with rural activities
7
, and peak
incidence in the 30 to 50 year age group
1-2,6
. The disease
has many clinical forms, particularly lymph node and
pulmonary involvements as well as mixed forms
1, 2, 8, 9
. One
of the early and more frequent manifestations is the
presence of mulberry-like ulcers on the oral mucous
membranes
2,7,10-11
.
Infection may remain subclinical, localized or may
occasionally disseminate
6,12
. Hematogenous
dissemination of paracoccidioidomycosis to abdominal
lymph nodes, spleen, liver, adrenal glands, skin, or brain
can result in life-threatening complications
1,4,9
. Adrenal
glands involvement has been documented and post-
mortem studies report adrenal abnormalities in 44 to 80%
of cases
13-15
. Paracoccidioidomycosis is regularly
associated with adrenal insufficiency in 10-15% of
symptomatic cases
14-16
.
Although the involvement of the adrenal glands for P.
brasiliensis is not uncommon, there is not many cases
reported Addison’s disease associated to oral
paracoccidioidomycosis. A case of oral
paracoccidioidomycosis with involvement of adrenal
glands is reported herein.
Clinical case
A 61-year-old male was referred to the Municipal Dentistry
Service of Campinas-SP, Brazil, in November 2001,
complaining about a painful ulcerative lesion on the right
posterior-lateral/venter tongue lasting 2 months. The
patient had a 3-week history of mild progressive darkening
of the skin, dysphagia and weight loss. He smoked for
more than 30 years.
On clinical examination, the patient had a 2.0 X 2.0 cm
ulcer on the right lateral/venter tongue. The ulcer had a
granular surface with little inflammatory halo (Figure 1).
With clinical diagnosis was squamous carcinoma, the
patient was submitted to an incisional biopsy. The
microscopic examination showed non-necrotizing
granulomas with abundant multinucleated giant cells in
the conjunctive tissue, and zones of
pseudoepitheliomatous hyperplasia (Figure 2). Yeast-like
organisms with thick capsules in multiple budding forms
were observed by special stain SPA (Schiff’s periodic acid).
The clinicopathological features allowed the diagnosis of
paracocidioidomycosis. After diagnosis, chest
radiographs were made and confirmed pulmonary
involvement.
The patient was referred to the Municipal Center of Infect
Disease for further management of his systemic disease.
At the moment, it was suspected involvement of the
adrenal glands due to the history of progressive skin
darkening, dysphagia and weight loss (Figure 3). After
hormonal level exams of adrenal glands, that showed low
basal steroid levels and lack of response to ACTH
(adrenocorticotropic hormone) therapy, the diagnosis of
Addison’s disease caused by P. brasiliensis was made.
The patient was treated with steroids, sulfa and, after 5
months, the oral lesion resolved, but the clinical features
of adrenal complications yet persist. The patient was not
returned to the Medical Service for follow-up.
Fig. 1. Ulcerative lesion in right lateral-posterior/venter tongue.
!
!
!
!
!
Fig. 2. Histological aspect of oral lesion. Observe area of focal
granulomatous reactions showing multinucleated giants cells with
P. brasiliensis within the cytoplasm (H.E, X 100).
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3. Fig. 3. Face of the patient. He had a history of mild progressive
darkening of the skin and weight loss.
Discussion
It is generally accepted that in typical Addison’s disease,
the destructive lesion of the adrenal glands must be of a
chronic progressive nature such as might be associated
with amyloidosis, tumor formation, tuberculosis, and other
infectious diseases
16-18
. Adrenal involvement by
granulomatous diseases is the main cause of the gland
insufficiency in Brazil
1,14
, but infectious forms of the
Addison’s disease are relatively rare in the United States
18
.
Among these, paracoccidioidomycosis is considered the
most prevalent systemic mycosis in Latin America
1,3,14
.
Paracoccidioides brasiliensis exhibits a high tropism for
the adrenal glands which results in a low hormone reserve
and, in more severe cases, in symptoms of primary adrenal
insufficiency
19
. Adrenal involvement has been
demonstrated in 21% to 80% of autopsy cases
20
.
Azevedo
21
, in 1934, was the first to report one case with
extensive necrotic changes in adrenal gland caused by P.
brasiliensis. Del Negro
14
, 1961, reported involvement of
the adrenal glands in 3 paracocidioidomycosis patients
autopsied in study with 27 individuals.
Several reports have described adrenal dysfunction in
paracocidioidomycosis. These studies usually focused on
cortisol responses to synthetic ACTH
(adrenocorticotropic hormone) administration and
established graded impairment of adrenal dysfunction
13-
14,22
. Because differing methodologies were used to
interpret the data, comparisons are difficult.
Adrenocortical hypofuction associated with disseminated
P. brasiliensis could be detected in 22% to 48% of patients,
with a 9% to 14% prevalence of symptomatic Addison’s
disease
14,19,22
. Colombo et al
4
, 1994, reported hypofunction
of adrenal glands in only 14% of patients with
disseminated paracoccidioidomycosis. The higher
prevalence of adrenocortical hypofunction is associated
with the disseminated forms of paracoccidioidomycosis;
however, the possibility of exclusive adrenal involvement
as the sole manifestation of the disease has been
demonstrated
14,16-17
.
The relationship between the pathogenetic factors of
paracocidioidomycosis and adrenocortical hormones has
not been explored. In recent years, many studies have
documented that numerous cytokine family members
influence the secretory activity of the hypothalamic-
pituitary-adrenal (HPA) axis, which generally inhibit or
modulate inflammation through the immunossuppressive
effects of the glucocorticoids
23
. More recently, the adrenal
androgen dehydroepiandrosterone sulfate (DHEA-S) was
implicated as an immunomodulator hormone
24
. Leal et al.
25
(2003) examined the functional status of adrenocortical
hormones and their relationship with inflammatory
cytokine patterns in patients with active
paracocidioidomycosis. Their findings demonstrate a
significant inverse correlation between DHEA-S and
interleucine-6 plasma levels in paracocidioidomycosis,
which may be of pathogenetic significance in this and
others inflammatory diseases
25
.
Although the typical oral paracoccidioidomycosis lesions
consist of multiples mulberry-like ulcers in palate, gums,
buccal mucosa, lips, and tongue, the patient reported
herein showed only one ulcerative lesion with
granulomatous surface and inflammatory halo. These
clinical features, associated with chronic smoking and
drinking habits, lead to a wrong clinical diagnosis of
squamous carcinoma. On the other hand, with definitive
diagnosis of paracoccidioidomycosis, it was possible to
suspect of adrenal glands involvement due to the patient
had history of mild progressive darkening of the skin,
dysphagia and weight loss.
Paracoccidioidomycosis is most relevant to dentistry
because lesions may involve especially the head and neck,
typically the oral and nasal mucosa, and facial skin
2
. In
spite of not being rare the involvement of the adrenal
glands for the P. brasiliensis, it was not possible to find
in the literature a similar case that the oral
paracoccidoidomycosis lesion provided the diagnosis of
mycosis disease disseminated with secondary Addison’s
disease caused by P. brasiliensis. The patient reported
herein received diagnosis of paracoccidioidomycosis and
Addison’s disease due to one oral lesion. It was confirmed
the value of dentistry on systemic diseases diagnosis.
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