Nama: Ni Wayan Ayu Sasmitha Utami

NIM: 20//KG/12202
Dosen Pembimbing : drg. Fimma Naritasari, MDSc

Curi DS, Leite-Ribeiro PM, Torregrossa VR, Vieira VC, Sarmento VA. Efficacy of imidazolquinoline
on treatment of condyloma acuminatum of the buccal mucosa. Spec Care Dentist. 2017
Jan;37(1):51-54.
Critical Appraisal
Efficacy of imidazolquinoline on treatment of condyloma acuminatum of the buccal mucosa
1. Karakteristik demografi pasien pada jurnal dideskripsikan namun tidak
terlalu lengkap. Pada jurnal tersebut tidak dicantumkan mengenai prognosis
pasien. Data yang terdapat pada karakteristik demografi pada jurnal tersebut
berupa :
a. Umur pasien : 25 tahun.
b. Jenis Kelamin : Laki-laki
c. Diagnosis : Condyloma Acuminata
d. Diagnostic Test : Dilakukan pengamatan IO dan Biopsi
e. Prognosis :-
“Patient FCCP is a 25-year-old, HIV positive male without clinical signs and symptoms
related to the virus who had a viral load of 21,370 copies/ml and a CD4 lymphocyte count
(LT-CD4 +) of 404 cells/mm³ and was not receiving antiretroviral therapy (ART). The
patient was referred to the Dental Care Service of Federal University of Bahia-Brazil in
October 2011 with injuries on his upper lip with an approximate a 1-year duration. On
clinical examination, extensive papillomatous proliferations of a warty surface that look
like cauliflower and had spread horizontally were observed . The patient had undergone a
biopsy on another service, which confirmed the histopathologic diagnostic of condyloma
acuminata.”
2. Patient’s History pada jurnal ini hanya dideskripsikan sebagai berikut :
“The patient started ART (Combivir, Ritonavir, and Lopinavir) in October 2013 after
presenting with a currently undetectable viral load and a CD4 cell count of 543 cells/mm³.
He has been without lesions for 2 years and is still under observation .”
3. Kondisi klinis pasien dijelaskan melalui hasil pemeriksaan intraoral yang
telah dilakukan operator berupa :
“ on clinical examination, extensive papillomatous proliferations of a warty surface that look
like cauliflower and had spread horizontally were observed”
4. Pada jurnal tersebut dideskripsikan mengenai diagnostic test untuk
mendapatkan diagnosis dari kasus tersebut. Deskripsi tesebut berupa :
“The patient reported having been treated with the application of caustic chemicals
(trichloroacetic acid) and cryotherapy with liquid nitrogen. He reported the reappearance
of the lesions after 30 days of treatment. The patient had undergone a biopsy on another
service, which confirmed the histopathologic diagnostic of condyloma acuminata. The
lesions gradually entered remission and there was no complain of persisted in the upper
labial mucosa. The lesion was then surgically excised under local anesthesia. The
specimen, sent for pathology analysis, confirmed the diagnosis of condyloma. In addition,
we found that the surgical specimen was negative for p16”
5. Pada jurnal tersebut tidak disebutkan mengenai efek samping dari prosedur
perawatan namun dijelaskan mengenai prosedur perawatan bedah, rute
administrasi obat dan dosis obat. Hal tersebut dipaparkan pada :
 “Considering the extent of the injury and its location, it was decided to use 5%
imidazolquinoline (cream) to avoid aesthetic problems resulting from surgical approaches.
Residual lesions, if they existed, could be surgically removed by a later procedure. The
drug was applied three times a week for 60 days. Before application, the patient was
instructed to dry the area. Then, a thin layer was applied to the injuries at night and was
considered to be active for approximately 6 hours. After this period, the area was washed
with soap and water to remove the residual cream. If there was a reaction to the drug, the
patient was instructed to contact the health care service. The protocol application was based
on the use of this medication for treatment of multifocal epithelial hyperplasia and genital
and perianal warts.” “The cream is used three times per week overnight and is applied until
the warts disappear or for a maximum of 16 weeks. If the imidazolquinoline is causing
local clinical signs of inflammation, it is advisable to interrupt the application until the
disappearance of side effects and then resume therapy. It is important that the patient has
been informed that the cream should be applied for at least 4 weeks to be effective”
6. jurnal ini dideskripsikan mengenai post intervention pasien disertai dengan
gambar kondisi post intervention. Hal tersebut dideskripsikan pada :
“During therapy, there was no erythema, edema and/or painful symptoms. At the end of
therapy (8 weeks), a single papule was present and was surgically removed, leaving
cosmetic damage. The patient is without recurrence for 2 years. This can be explained by
the effect of the drug on keratinocytes, as the treatment stimulates these cells to produce
interferon-α, an important cytokine in viral infections. This cytokine inhibits viral
replication and stimulates the induction of cytotoxic T cells.”
7. jurnal dipaparkan mengenai perawatan yang diambil untuk menghindari
adanya adverse event dari prosedur yang telah dilakukan oleh operator dari
jurnal ini yang dipaparkan pada kalimat :
“Considering the extent of the injury and its location, it was decided to use 5%
imidazolquinoline (cream) to avoid aesthetic problems resulting from surgical approaches.
Residual lesions, if they existed, could be surgically removed by a later procedure. The
drug was applied three times a week for 60 days. Before application, the patient was
instructed to dry the area. Then, a thin layer was applied to the injuries at night and was
considered to be active for approximately 6 hours”

8. Pada jurnal case report ini dipaparkan berupa latar belakang kasus,
perawatan dari kasus tersebut serta pembahasan dari kasus tersebut sehingga
case report ini bisa dijadikan acuan dalam mengambil keputusan jika
dihadapkan pada kasus yang serupa.
 EFFICACY OF IMIDAZOLQUINOLINE ON TREATMENT OF CONDYLOMA ACUMINATUM
CASE HISTORY REPORT
ABSTRACT
The condylomata acuminata is a benign
epithelial neoplasm induced by papillo-
mavirus, and it is characterized by the
proliferation of stratified squamous epi-
thelial tissue that affects the anogenital
and oral mucosa. It is considered to be
a sexually transmitted disease and has a
higher prevalence in individuals infected
with human immunodeficiency virus.
Various therapies have been used for
the removal of lesions, such as cryother-
apy, surgical laser and surgical excision,
which are painful and scarring. These
techniques, however, do not eliminate
the virus and relapses are common
shortly after treatment. The use of
immunomodulators has been proposed
to be an alternative treatment, as imida-
zolquinoline has been shown to be
effective in the treatment of lesions in
the anogenital region. However, its use
in the oral cavity has been the subject of
few reports in the literature. Thus, the
objective of this study is to describe a
case of warts in the labial mucosa of an
HIV positive patient using imidazolquin-
oline 5%.
KEY WORDS: condyloma
acuminatum, Imidazolquinoline
© 2016 Special Care Dentistry Association and Wiley Periodicals, Inc.
DOI: 10.1111/scd.12199
scd12199.indd 1
Efficacy of imidazolquinoline on
treatment of condyloma acuminatum
of the buccal mucosa
Davi Silva Carvalho Curi, DDS;1 Patrícia Miranda Leite-Ribeiro, DDS, MS,
PhD;2* Vinicius Rabelo Torregrossa, DDS, MS;3 Vinicius Costa Vieira, DDS;1
Viviane Almeida Sarmento, DDS, MS, PhD4
1DentistryDepartment, Hospital Universitario Professor Edgard Santos, Federal University of Bahia
(UFBA), Brazil; 2Professor at Dentistry Department, Hospital Universitario Professor Edgard Santos,
Federal University of Bahia (UFBA), Brazil; 3University of Campinas, Brazil; 4Coordinator of Dentistry
Department, Hospital Universitario Professor Edgard Santos, Federal University of Bahia (UFBA), Brazil
*Corresponding author e-mail: patricia.leiteribeiro@gmail.com
Spec Care Dentist XX(X): 1-4, 2016
Introd uct ion
Condyloma acminata is a proliferation of the stratified squamous epithelium and is
induced by papillomavirus (HPV), which affects the anogenital region and oral mucosa.
It is considered to be a sexually transmit- not receiving antiretroviral therapy, 15%
ted disease (STD) and represents 20% of in those receiving antiretroviral therapy
all STDs.1 other than HAART and 23% in those
HPVs belong to the family receiving HAART for a time interval of
Papillomaviridae and infect the skin and 4 years between 1996 and 1999.6
mucous membranes through abrasions to Therefore, these lesions are considered to
the skin and mucosa during sex, by auto- be indicative of a good HIV infection
inoculation or contact with contaminated prognosis. However, other studies have
objects, allowing access of the virus to the suggested that a reduction in the viral
basal layer cells responsible for epithelial load, not HAART itself, may be responsi-
renewal for preserving mitotic capacity.1 ble for the increase in oral warts in
A higher prevalence of HPV-related HIV-epatients. In addition, oral HPV
injuries is observed in patients infected infection in HIV positive individuals is
with human immunodeficiency virus relate d to increasing age, male gender,
(HIV).1,2 Studies have shown an associa- multiple partners and low CD4 cell
tion between HIV and oral HPV lesions.3–5 counts (<200 cells/ml).7
With the advent of highly active The treatment of HPV lesions should
antiretroviral therapy (HAART), the be individualized and aims to remove the
prevalence of oral HPV lesions has visible lesion, although this is does not
increased significantly.4 In the study by effectively eradicate the virus.1,8 Several
Greenspan et al. (2001) that assessed the sessions of different therapeutic modalities
prevalence of oral warts in 1280 patients for complete resolution of the lesions may
after HAART, the prevalence of oral warts be necessary. The conventional chemical
increased from less than 10% in 1990 to treatment is the destruction of the lesion
over 20% in 1999. The prevalence of oral with a topical application of podophyllin,
warts was only 5% in subjects who were 5-fluorouracil, Bi/trichloroacetic acid and
Spec Care Dentist XX(X) 2016 1
16/09/16 11:19 AM
 EFFICACY OF IMIDAZOLQUINOLINE ON TREATMENT OF CONDYLOMA ACUMINATUM
podophyllotoxin. Other methods include
physically destructive cryosurgery, high
intensity laser cauterization and surgical
excision. These procedures are painful,
result in scarring and may require the use
of anesthesia. Additionally, relapses are
common shortly after treatment.
Modulation of the immune response
by a systemic, topical, and intralesional
drug is an alternative therapy.8 Several
case reports have explored the use of
therapeutic options for the treatment of
oral HPV infections in HIV-seropositive
individuals, such as topical 1% to 3%
Cidofovir, interferon-α intralesional and
oral cimetidine, all with complete remis-
sion of the lesion and with limited
recurrence in very small numbers of
patients.9
Another pharmacotherapy option is
imidazolquinoline, which was approved
by the Food and Drug Administration
(FDA) in 1997 for the treatment of exter-
nal and perianal genital warts in
adults8,10,11 due to its proven efficacy in
randomized, double-blind studies, espe-
cially at a dose of 5%.12 Its use results in
the successful treatment of injuries
resulting from viral infections, such as
condyloma in adults. Some case reports
suggest its effectiveness in eradicating
oral HPV infe ctions.13,14 Rinne
et al.(2000) found an extensive decrease
in lip papillomatosis, which was previ-
ously resistant to cryosurgery and
interferon topic, after treatment with 5%
imidazolquinoline cream in three HIV
positive women.15
The cream is used three times per
week overnight and is applied until the
warts disappear or for a maximum of
16 weeks. If the imidazolquinoline is
causing local clinical signs of inflamma-
tion, it is advisable to interrupt the
application until the disappearance of side
effects and then resume therapy. It is
important that the patient has been
informed that the cream should be applied
for at least 4 weeks to be effective.10
Imidazolquinoline immunomodulates
the innate immune response through its
activation of dendritic cells, mac-
rophages, and other cells by binding to
the TLR-7 receptor of these cells, induc-
ing interferon (IFN-α) production, a
2 Spec Care Dentist XX(X) 2016
scd12199.indd 2
cytokine produced by keratinocytes and
other cells after viral infection, and pro-
inflammatory cytokines.16 In addition to
the innate response, imidazolquinoline
can also help induce specific immune
responses. In vitro, Langerhans cells
exposed to this product enhanced their
capacity to induce the proliferation of
Tlymphocytes.17 Stanley (2002) com-
pared imidazolquinolin to a placebo in
genital warts and showed that it was sig-
nificantly more effective than the placebo Figure 1. Clinical aspect.
by activating macrophages and directly
inducing Th1-type cytokines, including
later procedure. The drug was applied
Interleukin-12.16
three times a week for 60 days. Before
The use of this medicine in oral
application, the patient was instructed to
mucosa lesions has been described in few
dry the area. Then, a thin layer was
reports. Thus, the aim of this study is to
applied to the injuries at night and was
report a case of condyloma acuminata in
considered to be active for approximately
the labial mucosa, which was treated
6 hours. After this period, the area was
with 5% imidazolquinoline.
washed with soap and water to remove
the residual cream. If there was a reac-
Case r ep or t tion to the drug, the patient was
instructed to contact the health care ser-
Patient FCCP is a 25-year-old, HIV posi-
vice. The protocol application was based
tive male without clinical signs and
on the use of this medication for treat-
symptoms related to the virus who had a
ment of multifocal epithelial
viral load of 21,370 copies/ml and a CD4
hyperplasia13 and genital and perianal
lymphocyte count (LT-CD4 +) of 404
warts.17
cells/mm³ and was not receiving antiret-
The lesions gradually entered remis-
roviral therapy (ART). The patient was
sion and there was no complain of
referred to the Dental Care Service of
persisted in the upper labial mucosa. The
Federal University of Bahia-Brazil in
lesion was then surgically excised under
October 2011 with injuries on his upper
local anesthesia. The specimen, sent for
lip with an approximate a 1-year dura-
pathology analysis, confirmed the diag-
tion. On clinical examination, extensive
nosis of condyloma. In addition, we
papillomatous proliferations of a warty
found that the surgical specimen was
surface that look like cauliflower and had
negative for p16.
spread horizontally were observed
The patient started ART (Combivir,
(Figure 1). The patient reported having
Ritonavir, and Lopinavir) in October
been treated with the application of caus-
2013 after presenting with a currently
tic chemicals (trichloroacetic acid) and
undetectable viral load and a CD4 cell
cryotherapy with liquid nitrogen. He
count of 543 cells/mm³. He has been
reported the reappearance of the lesions
without lesions for 2 years and is still
after 30 days of treatment. The patient
under observation (Figure 2).
had undergone a biopsy on another ser-
vice, which confirmed the
histopathologic diagnostic of condyloma
acuminata. C oncl us ion
Considering the extent of the injury The case reported occurred in an individ-
and its location, it was decided to use 5% ual male who was 25 years old and HIV
imidazolquinoline (cream) to avoid aes- positive. The literature indicates that oral
thetic problems resulting from surgical HPV infection in HIV+ individuals is
approaches. Residual lesions, if they related to increased age, male gender and
existed, could be surgically removed by a the advent of HAART.1,2,4 This patient,
Efficacy of imidazolquinoline on treatment of condyloma acuminatum
16/09/16 11:19 AM
 EFFICACY OF IMIDAZOLQUINOLINE ON TREATMENT OF CONDYLOMA ACUMINATUM
Figure 2. After treatment.
however, had not initiated HAART
because his viral load and the LT-CD4 +
were 21,370 copies/ml and 404 cells/
mm³, respectively, and he had no clinical
signs or symptoms related to the virus.
However, recent studies have shown a
reduction in morbidity, mortality and
HIV transmission with the early initia-
tion of antiretroviral therapy in a
symptomatic patients (LT-CD4 ≤ 500
cells/mm³).18,19
An increased prevalence of HPV
lesions in HIV positive patients has been
observed following the advent of
HAART6. This is, in part, due to the
Immune Reconstitution Inflammatory
Syndrome (IRIS). It is an adverse effect
of HAART, which induces an overactive
inflammatory response, causing the loss
of immunomodulatory mechanisms and
the antigen-specific response, conse-
quently leading to the appearance of
prior subclinical infections or pre-exist-
ing opportunistic infections, such as
condyloma acuminata.20 However, our
patient was not on ART at the time of the
appearance of lesions. This may be
related to the active state of his immune
system, which acted as if he was using
ART because the infection of keratino-
cytes by HPV depends on three factors:
cell permeability, the type of HPV and
the immune status of the host.1
Clinically, the lesions had the classic
features of condyloma acuminata, and
the histological features were also con-
sistent with condyloma acuminata. We
observed papillomatous formation lined
by squamous epithelium with p16 test
was negative. Although the literature
proposes that the overexpression of this
Curi et al. Spec Care Dentist XX(X) 2016 3
scd12199.indd 3
biomarker improves the specificity of a
condyloma acuminata diagnosis, it does
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