1. Braz J Oral Sci. April/June 2004 - Vol. 3 - Number 9
Addison’s disease associated to
paracocidioidomycosis
Claudio Maranhão Pereira3
Silmara Regina Silva1 Abstract
Priscila Spaziane Camargo1 Paracoccidioidomycosis is a deep mycosis caused by the
Andrea Mantesso2 Paracoccidioides brasiliensis and it has been considered the most fre-
Rodrigo Calado Nunes Souza 1 quent systemic mycosis in Latin America. Mulberry-like ulcers on the
1
Dentistry Section, Municipal Healthy Service, oral mucous membranes are one of the earliest manifestations of the
Campinas-SP, Brazil disease. Infection may remain subclinical, localized or disseminate oc-
2
Oral Pathology, São Leopoldo Mandic Dental casionally.
Research Institute, Campinas-SP, Brazil Adrenal involvement by granulomatous diseases is the main cause of
3
Oral Pathology, School of Dentistry of this gland insufficiency in Brazil. The aim of this study is to report one
Piracicaba, UNICAMP, São Paulo, Brazil
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.
Received for publication: September 30, 2003 Key Words:
Accepted: March 2, 2004
Addison’s disease, paracoccidioidomycosis, adrenal glands.
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: claudiomaranhao@hotmail.com
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2. Braz J Oral Sci.3(9):475-478 Addison’s disease associated to paracocidioidomycosis
Introduction were observed by special stain SPA (Schiff’s periodic acid).
Paracoccidioidomycosis (South America blastomycosis) The clinicopathological features allowed the diagnosis of
is a chronic mycosis disease caused by the dimorphic paracocidioidomycosis. After diagnosis, chest
fungus Paracoccidioides brasiliensis 1-2 . Geographic radiographs were made and confirmed pulmonary
fungal distribution is restricted to Latin America where it involvement.
is considered the most prevalent systemic mycosis 3-5. It The patient was referred to the Municipal Center of Infect
is still relatively unknown in the United States and Disease for further management of his systemic disease.
Europe 4,6 . At the moment, it was suspected involvement of the
P. brasiliensis may grow in the soil, in water, on plants in adrenal glands due to the history of progressive skin
rural areas, and reaches the human host by the inhalation darkening, dysphagia and weight loss (Figure 3). After
of airbone propagules 5. Ninety per cent of cases have hormonal level exams of adrenal glands, that showed low
occurred in males patients with rural activities7, and peak basal steroid levels and lack of response to ACTH
incidence in the 30 to 50 year age group1-2,6. The disease (adrenocorticotropic hormone) therapy, the diagnosis of
has many clinical forms, particularly lymph node and Addison’s disease caused by P. brasiliensis was made.
pulmonary involvements as well as mixed forms1, 2, 8, 9. One The patient was treated with steroids, sulfa and, after 5
of the early and more frequent manifestations is the months, the oral lesion resolved, but the clinical features
presence of mulberry-like ulcers on the oral mucous of adrenal complications yet persist. The patient was not
membranes 2,7,10-11. returned to the Medical Service for follow-up.
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.
Fig. 1. Ulcerative lesion in right lateral-posterior/venter tongue.
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 Fig. 2. Histological aspect of oral lesion. Observe area of focal
pseudoepitheliomatous hyperplasia (Figure 2). Yeast-like granulomatous reactions showing multinucleated giants cells with
organisms with thick capsules in multiple budding forms P. brasiliensis within the cytoplasm (H.E, X 100).
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3. Braz J Oral Sci.3(9):475-478 Addison’s disease associated to paracocidioidomycosis
P. brasiliensis could be detected in 22% to 48% of patients,
with a 9% to 14% prevalence of symptomatic Addison’s
disease14,19,22. Colombo et al4, 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 glucocorticoids23. More recently, the adrenal
androgen dehydroepiandrosterone sulfate (DHEA-S) was
implicated as an immunomodulator hormone24. Leal et al.25
Fig. 3. Face of the patient. He had a history of mild progressive (2003) examined the functional status of adrenocortical
darkening of the skin and weight loss.
hormones and their relationship with inflammatory
cytokine patterns in patients with active
Discussion paracocidioidomycosis. Their findings demonstrate a
It is generally accepted that in typical Addison’s disease, significant inverse correlation between DHEA-S and
the destructive lesion of the adrenal glands must be of a interleucine-6 plasma levels in paracocidioidomycosis,
chronic progressive nature such as might be associated which may be of pathogenetic significance in this and
with amyloidosis, tumor formation, tuberculosis, and other others inflammatory diseases 25 .
infectious diseases 16-18 . Adrenal involvement by Although the typical oral paracoccidioidomycosis lesions
granulomatous diseases is the main cause of the gland consist of multiples mulberry-like ulcers in palate, gums,
insufficiency in Brazil 1,14 , but infectious forms of the buccal mucosa, lips, and tongue, the patient reported
Addison’s disease are relatively rare in the United States18. herein showed only one ulcerative lesion with
Among these, paracoccidioidomycosis is considered the granulomatous surface and inflammatory halo. These
most prevalent systemic mycosis in Latin America1,3,14. clinical features, associated with chronic smoking and
Paracoccidioides brasiliensis exhibits a high tropism for drinking habits, lead to a wrong clinical diagnosis of
the adrenal glands which results in a low hormone reserve squamous carcinoma. On the other hand, with definitive
and, in more severe cases, in symptoms of primary adrenal diagnosis of paracoccidioidomycosis, it was possible to
insufficiency 19 . Adrenal involvement has been suspect of adrenal glands involvement due to the patient
demonstrated in 21% to 80% of autopsy cases 20 . had history of mild progressive darkening of the skin,
Azevedo 21, in 1934, was the first to report one case with dysphagia and weight loss.
extensive necrotic changes in adrenal gland caused by P. Paracoccidioidomycosis is most relevant to dentistry
brasiliensis. Del Negro 14, 1961, reported involvement of because lesions may involve especially the head and neck,
the adrenal glands in 3 paracocidioidomycosis patients typically the oral and nasal mucosa, and facial skin2. In
autopsied in study with 27 individuals. spite of not being rare the involvement of the adrenal
Several reports have described adrenal dysfunction in glands for the P. brasiliensis, it was not possible to find
paracocidioidomycosis. These studies usually focused on in the literature a similar case that the oral
cortisol responses to synthetic ACTH paracoccidoidomycosis lesion provided the diagnosis of
(adrenocorticotropic hormone) administration and mycosis disease disseminated with secondary Addison’s
established graded impairment of adrenal dysfunction 13- disease caused by P. brasiliensis. The patient reported
14,22
. Because differing methodologies were used to herein received diagnosis of paracoccidioidomycosis and
interpret the data, comparisons are difficult. Addison’s disease due to one oral lesion. It was confirmed
Adrenocortical hypofuction associated with disseminated the value of dentistry on systemic diseases diagnosis.
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4. Braz J Oral Sci.3(9):475-478 Addison’s disease associated to paracocidioidomycosis
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