Photodiagnosis and Photodynamic Therapy 37 (2022) 102648

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Photodiagnosis and Photodynamic Therapy

journal homepage: www.elsevier.com/locate/pdpdt

Case report

Photodynamic therapy in the treatment of oral lesions caused

by paracoccidiomycosis
Danila Silvana de Alexandria Santos a, Gustavo Souza Galvão a, Priscila Fernandes Ribas a,
Maria Paula Siqueira de Melo Peres a, Juliana Bertoldi Franco a, b, *
a
Department of Dentistry, Central Institute, Clinical Hospital of Medical School of the University of São Paulo, São Paulo, SP, Brazil
b
Department of Dentistry, Auxiliary Hospital of Suzano - Clinical Hospital of Medical School of the University of São Paulo - São Paulo, SP, Brazil

A R T I C L E I N F O A B S T R A C T

Keywords: Paracoccidioidomycosis (PCM) is an endemic disease caused by the dimorphic fungus Paracocdioides brasiliensis
Paracoccidioidomycosis and Paracoccidioides lutzii. Oral ulcers are usually the first clinical signs of the disease. As it is a systemic fungal
Photodynamic Therapy disease, local treatments are considered complementary, such as photodynamic therapy (aPDT). We present a
Oral and Maxillofacial Pathology
patient with ulcerated lesions in the oral cavity of about 6 months duration. The pain complaint in the
Oral Medicine
Dental Care
oropharynx led to a reduction in food acceptance and a weight loss of around 40 kg. He underwent biopsy of the
lip lesion, and the histopathological report described yeast with multiple buds compatible with PMC. Our team
opted for treatment with aPDT sessions. Two sessions were carried out in the ward and six in the ICU, showing
satisfactory results in the remission of ulcerated lesions associated with PCM as well as the painful symptoms in
the oral cavity. Also, the patient underwent Amphotericin B and Sulfamethoxazole-trimethoprim. We believe
that the association of aPDT with pharmacological therapy possibly accelerated the repair process of oral lesions,
as well as providing fungal lesion decontamination, improving progressively the healing of oral lesions.

1. Introduction
Paracoccidioidomycosis (PCM) is an endemic disease caused by the
dimorphic fungus Paracocdioides brasiliensis and Paracoccidioides lutzii.
The disease is more prevalent in men, with a mean age of 51.3 years. In
Brazil, the south and southeast are the regions with the highest inci­
dence, and mortality in endemic areas is around 20% [1]. The disease
sets in when the spores are inhaled, mainly affecting the lungs. Other
regions and organs are affected by lympho-hematological dissemina­
tion, including the oral mucosa [2].
PCM can be classified as acute (or subacute or juvenile) and chronic
(unifocal or multifocal). In the first one, the manifestation occurs in
children and young people up to 30 years of age, of both sexes. The
chronic form affects adults over 30 years of age, with a 15:1 male-to-
female ratio [1–4]. In both forms, the treatment must be done individ­
ually, using antifungal agents and systemic antibiotics, taking into ac­
count the morbidities, nutritional status and administration of
medications for continuous use [4].
Manifestations in the oral mucosa are usually the first clinical signs
of the disease, aiding in the clinical diagnosis, which is often delayed.
Due to the ulcerated aspect, lesions associated with PCM have squamous
cell carcinoma as a differential diagnosis [2,3]. The diagnosis is
confirmed through incisional biopsies, showing pseudoepitheliomatous
hyperplasia, epithelial discontinuity, chronic inflammatory infiltrate
with multinucleated giant cells. Special staining techniques such as
Periodic Acid Schiff (PAS) and Grocott-Gomori methenamine silver can
identify Paracocdioides brasiliensis yeasts in biopsied tissues, which pre­
sent multiple daughter buds in a so-called aspect of “Mickey Mouse ears”
[1].
As it is a systemic fungal disease, local treatments are considered
complementary, such as the photodynamic therapy (aPDT). In addition
to being potentially effective in healing and analgesia, aPDT acts to
eliminate pathogenic microorganisms, with the advantage of not
inducing microbial resistance [5,6].
The therapy is based on the application of a photosensitizing agent
on the injured tissue followed by low power laser emission on the region.
The interaction generates free radicals and oxidation of the plasma
membrane of microorganisms, providing antimicrobial and antifungal

* Corresponding author at: Department of Dentistry, Central Institute, Clinical Hospital of Medical School of the University of São Paulo, Av. Dr. Enéas de Carvalho
Aguiar, 255, 6 Andar, Sala 02, São Paulo, SP 05402-000, Brazil.
E-mail addresses: priscila.ribas@hc.fm.usp.br (P.F. Ribas), maria.peres@hc.fm.usp.br (M.P.S.M. Peres), juliana.franco@hc.fm.usp.br (J.B. Franco).

https://doi.org/10.1016/j.pdpdt.2021.102648
Received 16 July 2021; Received in revised form 18 November 2021; Accepted 19 November 2021
Available online 22 November 2021
1572-1000/© 2021 Elsevier B.V. All rights reserved.

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D.S.A. Santos et al. Photodiagnosis and Photodynamic Therapy 37 (2022) 102648

Fig. 1. 1A- Initial photo of the patient showing extensive granulomatous ulcers lesion with fibrinoid secretion in vermilion of the left lower lip and tongue apex; 1B-
Patient in the ICU, with orotracheal intubation, and left lower lip lesion after 2 sessions of aPDT; 1C- Clinical photo of the lip lesion after 5 sessions of aPDT; 1D-
Healing of the lesion on the left lower lip after 8 sessions of aPDT, followed by hospital discharge.

activity without harming healthy host cells [6].
The aim of this paper is to report a case of PCM with extensive oral
manifestations in which aPDT was used as an adjuvant treatment to
systemic pharmacological treatment, with positive results, during the
patient’s hospitalization in the Intensive Care Unit (ICU).
2. Case report
A 41-year-old caucasian male patient, smoker and chronic drinker
for 20 years, presented with ulcerated lesions in the oral cavity for about
6 months, initially in the left buccal mucosa and progressing to the lower
lip, with strong intensity painful symptoms. Due to the pain complaint in
the oropharynx, the patient reported a reduction in food acceptance,
leading to a weight loss of around 40 kg.
He sought medical care in his city in Paraná, Brazil, where a chest X-
ray was performed, suggesting pulmonary metastasis, so being referred
for follow-up with an oncologist. He was transferred to the Clinical
Hospital of Medical School of the University of São Paulo (HCFMUSP)
and was admitted for investigation due to a likely neoplasm of the oral
cavity. A computed tomography (CT) scan of the neck, chest and
abdomen was performed, which showed multiple lung lesions, lymph
node enlargement and possibly cervical abscess. He underwent to a bi­
opsy of the lip lesion, and the histopathological report described yeasts
with multiple buds compatible with Paracoccidioidomycosis.
During hospitalization, the patient complained of pain in the mouth
due to oral lesions, so he was evaluated by the Dental team. On intraoral
clinical examination, extensive granulomatous ulcers with fibrinoid
secretion were observed in the left buccal mucosa (Fig. 1A), which
extended to the mucosa and vermilion of the lower lip, hard palate,
edges and apex of the tongue. In addition, the patient presented
generalized periodontal disease and poor oral hygiene.
Upon the diagnosis of PCM, our team opted for treatment with aPDT
sessions, performed for 8 days. In order to do that, methylene blue at
0.01% was applied over all lesions and, after 5 min (time pre-
irradiation), the EC® laser device Therapy (DMC, São Carlos, SP,
Brazil) was used at 660 nm, on contact mode, point by point, with 100
mW, 178 J/cm2, 6 J, and 60 s per point5. Oral hygiene with 0.12%
chlorhexidine and continuous lip hydration with petroleum jelly and
lanolin were established. Also, the patient used Amphotericin B and
Sulfamethoxazole-trimethoprim [4].
After four days in the hospital, the patient presented desaturation,
tachycardia, bradypnea, evolving with a lowered level of consciousness.
The patient was transferred to the ICU, requiring orotracheal intubation
(Fig. 1B). Hospitalization in the ICU lasted twenty-three days, pro­
gressing satisfactorily, and extubation was performed on the eighteenth
day (Fig. 1C). Afterwards, follow-up was carried out in the ward, and the
hospital discharge occurred after forty-five days of hospitalization
(Fig. 1D). In total, two sessions of aPDT were carried out in the ward and
six in the ICU, showing satisfactory results in the remission of ulcerated
lesions associated with PCM as well as the painful symptoms in the oral
cavity.

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D.S.A. Santos et al.
3. Discussion
The reported case refers to a male individual, in his fifth decade of
life, smoker and drinker, residing in an endemic area for PCM, therefore
fitting into the risk group for Paracoccidioidomycosis [1,2]. The patient
presented classical manifestations of the multifocal chronic form, such
as pulmonary involvement, dyspnea, odynophagia, weight loss,
lymphadenopathy, manifestations in the oral mucosa and changes in the
level of consciousness, requiring treatment in the hospital environment
as well as in the ICU [2–4].
The treatment included intravenous use of amphotericin B associated
with sulfamethoxazole-trimethoprim, being considered the preferred
treatment since 1958 for the treatment of the most complex cases of
PCM, besides to ICU support [4].
The similarity between the presented case and a series study of six
confirmed cases of PCM is highlighted, in which five cases had squamous
cell carcinoma as differential diagnosis [2]. In another study with three
cases of PCM, debilitating oral lesions were also observed, with com­
plete healing of the lesions and formation of fibrosis along the oral
mucosa after aPDT protocol [5]. Nevertheless, there is a lack of ran­
domized controlled trials in the literature. Thus, it is possible to state
that the evidence for the use of aPDT as an adjuvant therapy for oral
lesions caused by PCM is currently based on case reports.
The aPDT is considered a non-invasive, local, painless procedure,
which has the advantages of tissue biostimulation, accelerating the
repair process and promoting analgesia, in association with antimicro­
bial and antifungal activity. It is considered the treatment of choice for
patients with oral lesions arising from opportunistic fungal or viral in­
fections, helping to reduce the administration of systemic medications.
In the current case, aPDT was introduced as an adjuvant and essential
treatment due to the seriousness of the case, and also because of the
great extension of the oral lesions.
We believe that the association of aPDT with pharmacological
therapy accelerated the repair process of oral lesions, as well as
providing fungal lesion decontamination, improving progressively the
healing of oral lesions. We emphasize that when the patient was
responsive, he reported a significant improvement in pain after the
application of aPDT, enabling oral feeding. Upon hospital discharge, the
patient had complete remission of the granulomatous ulcers present in
the oral mucosa.
Given the above, it can be concluded that the role of the dentist is
extremely important for the diagnosis of oral lesions and the institution
of treatments for serious diseases, mainly those of low invasiveness and
with restorative and antimicrobial characteristics, providing analgesia
and contributing to the recovery of the patient’s general health.
Furthermore, we encourage future prospective studies with a placebo
group in order to compare aPDT with other adjuvant therapies for PMC
with oral manifestation.
Ethical statement
No ethical statement will be required for this manuscript.
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Photodiagnosis and Photodynamic Therapy 37 (2022) 102648
Financial disclose
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
CRediT authorship contribution statement
Danila Silvana de Alexandria Santos: Writing – original draft.
Gustavo Souza Galvão: Writing – original draft, Writing – review &
editing, Investigation, Methodology. Priscila Fernandes Ribas: Su­
pervision, Methodology, Investigation, Conceptualization. Maria Paula
Siqueira de Melo Peres: Conceptualization, Investigation, Methodol­
ogy, Supervision. Juliana Bertoldi Franco: Writing – original draft,
Supervision, Methodology, Investigation, Conceptualization.
Declaration of Competing Interest
All authors declare that they have no conflict of interest.
Acknowledgement
We would like to offer our gratitude to all the colleagues at the
Department of Dentistry, Critical Care Medicine and Infectology of
Clinical Hospital of Medical School of the University of São Paulo for
their helpful discussion and assistance.
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