CLINICAL ▲ CASES
Treatment of human papillomavirus in childhood with
Tratamento do papiloma vírus humano na infância com creme de
Abstract: In children, lesions caused by the human papillomavirus (HPV) constitute a significant epidemi- ological issue and a therapeutic dilemma, particularly in the case of anogenital warts. The treatment of anogenital warts in children is a challenge, since standard treatments are generally painful and require the patient to be anesthetized. Imiquimod, a topical immune response modifier, constitutes an alternative ther- apeutic agent for the treatment of HPV. The present report describes four cases in which treatment with topically applied imiquimod 5% cream was implemented with successful results. Keywords: Aminoquinolines; Human papillomavirus 6; Human papillomavirus 11; Interferon inducers; Papillomavirus infections Resumo: Lesões decorrentes da infecção pelo papilomavírus humano na infância, em especial as verrugas anogenitais, são um importante problema epidemiológico e terapêutico. O tratamento das verrugas anogenitais na infância é um desafio terapêutico. Os tratamentos convencionais geralmente são dolorosos e necessitam de anestesia geral. O imiquimode, um imunomodulador tópico, constitui uma alternativa te- rapêutica. Serão descritos quatro casos tratados com sucesso utilizando creme de imiquimode a 5% aplica- do topicamente. Palavras-chave: Aminoquinolinas; Indutores de interferon; Infecções por papillomavirus; Papillomavirus 6 humano; Papillomavirus 11 humano
Received on 02.07.2009. Approved by the Advisory Board and accepted for publication on 31.07.2009. * Study conducted at the Outpatient Clinic of Sexually Transmitted Diseases, Department of Clinical Dermatology, Teaching Hospital, FAMUSP, São Paulo, SP, Brazil.
Conflict of interest: None / Conflito de interesse: Nenhum
Financial funding: None / Suporte financeiro: Nenhum
Preceptor, Dermatology Department of the Teaching Hospital, School of Medicine, University of São Paulo (FMUSP), São Paulo, SP, Brazil.
Currently participating in a doctoral program at the Department of Dermatology, School of Medicine, University of São Paulo (FMUSP). Collaborating physician at the Department of Dermatology, School of Medicine, University of São Paulo (FMUSP), São Paulo, SP, Brazil.
Masters degree in Dermatology from the Department of Dermatology, School of Medicine, University of São Paulo (FMUSP). Physician, Department of Dermatology of the Teaching Hospital, School of Medicine, University of São Paulo (FMUSP), São Paulo, SP, Brazil.
Doctorate degree in Medicine from the Department of Dermatology, School of Medicine, University of São Paulo (FMUSP). Assistant physician, Department of Clinical Dermatology and investigator at the Medical Research Laboratory, LIM 53, of the Teaching Hospital, School of Medicine, University of São Paulo (FMUSP), São Paulo, SP, Brazil.
Doctorate degree in Medicine from the Department of Dermatology, School of Medicine, University of São Paulo (FMUSP). Faculty, Dermatology Department, University of Campinas (UNICAMP). Head of the Division of Sexually Transmitted Diseases/AIDS of the Brazilian Society of Dermatology. Professor of the Department of Dermatology, School of Medicine, University of São Paulo (FMUSP), São Paulo, SP, Brazil.
2010 by Anais Brasileiros de Dermatologia
An Bras Dermatol. 2009;84(5):549-53.Brandt HRC, Fernandes JD, Patriota RCR, Criado PR, Belda W JrINTRODUCTION Case 2
Lesions resulting from the human papillo-
A one-year old male patient. His mother report-
mavirus infection, particularly genital warts, in child-
ed multiple perianal lesions of six months’ duration.
hood constitute a significant epidemiological issue and
Skin-colored papules were found in the perianal
a therapeutic dilemma. 1 The principal sites affected by
region (Figure 2). Previous treatment with 25%
the human papillomavirus (HPV) in children are the
podophyllin was unsuccessful. The child was born at
extremities and the face, anogenital warts being less
term following an uncomplicated vaginal delivery. His
common in childhood. 2 The mode of HPV transmis-
parents had no HPV-associated lesions.
sion remains controversial, but includes perinataltransmission, auto- and hetero-inoculation, sexual
abuse and possibly indirect transmission via fomites. 3
A two-year old girl. Her mother reported geni-
Anogenital lesions detected during a child’s first year
tal lesions of four months’ duration. Multiple skin-
of life are generally acquired perinatally. Nevertheless,
colored papules were found in the vulvar and perianal
doubts persist with respect to the origin of new lesions
region. The child was born at term following an
that appear between the first and third years of life. 4
uncomplicated vaginal delivery. Gynecological exami-
Treatment of extensive condylomatous lesions
nation revealed signs of a ruptured hymen and other
in childhood represents a therapeutic problem.
evidence of vaginal trauma. Following meticulous
Ablative procedures and laser surgery are painful and
evaluation, signs of sexual abuse were detected.
usually require general anesthesia. Topicalimiquimod 5% cream has been successfully used for
the treatment of condyloma acuminata in adults; how-
An 18-month old girl. Her mother reported gen-
ever, its use in children has yet to be established. 5
ital lesions of six months’ duration. Multiple skin-col-ored papules were found in the perianal region. The
child was born at term following an uncomplicated
vaginal delivery. Gynecological examination showed
A two-year old boy. His mother reported dis-
no abnormalities. Past history of sexual abuse.
seminated perianal lesions over the previous 12
A virological study of the lesions in the first
months, increasing in number and size. Multiple con-
three patients using polymerase chain reaction (PCR)
fluent brownish papules were observed, affecting the
resulted in positivity for HPV-6 and HPV-11 in all three
scrotum and perineal and inguinal regions (Figure 1).
cases. PCR was not performed in case 4. In all four
Previous treatment with 70% trichloroacetic acid was
cases, histopathology was compatible with condyloma.
unsuccessful. The child had been born at term follow-
Other findings included papillomatosis and acantho-
ing an uncomplicated vaginal delivery. His mother
sis, thickening and lengthening of the skin ridges, asso-
reported having had genital warts during pregnancy.
ciated with koilocytosis. Serology for syphilis, hepati-
The father was evaluated and no evidence was found
tis B and C and HIV was negative in all four cases.
of any genital lesions or extragenital warts.
The four cases were treated topically with
FIGURE 1: Case 1. Multiple brownish, confluent papules affecting FIGURE 2: Case 2. Multiple papules converging in skin-colored
the scrotum, perianal and inguinal regions, prior to treatment
plaques in the perianal region, prior to treatment
An Bras Dermatol. 2010;85(4):549-53.Treatment of human papillomavirus in childhood with imiquimod 5% cream
imiquimod 5% cream applied at home three times a
or trichloroacetic acid and podophyllotoxin. Methods
week. Complete regression of the lesions occurred
of physical destruction of lesions include cryotherapy,
after three weeks of use in cases 1 (Figure 3) and 3, and
laser, electrocauterization and surgical excision. 10
after four weeks in cases 2 and 4 (Figure 4). Treatment
Physical methods are often painful, may result in scar-
was continued for a total of six weeks in all cases. Only
ring and require the use of anesthesia. Recurrence of
one adverse event was recorded, consisting of moder-
the lesions is common. These repeated and painful
ate erythema on the perilesional skin identified in case
applications on the genitalia of a child may lead to psy-
1; however, the condition improved as treatment pro-
gressed. After six months of follow-up, no new clinical
Treatments based on the chemical or physical
lesions were found in any of the four cases.
destruction of the infected keratinocytes do notdirectly inhibit the infection or viral replication. Each
therapeutic option has its own inherent advantages
In adults, the transmission of genital warts
and disadvantages, and there is no medication up to
occurs mainly by sexual contact. Genital warts in
the present time that effectively eliminates HPV. 12
childhood may be acquired through nonsexual con-
The innate immune system, which defends the
tact. Condyloma acuminatum has been described in
host against viruses, is composed of natural killer cells
1-2% of cases of child sexual abuse, and 50-75% of the
and activated macrophages. Viral infection of the lym-
cases of genital warts in children are a consequence of
phocytes results in the production of antiviral
cytokines, the interferons, which activate various
associated with child sexual abuse more frequently
mechanisms that act against the virus in cells that are
than subtypes 2 and 3. 7 Perinatal transmission of gen-
not yet infected, rendering them resistant to infection.
ital warts from infected mothers to the external geni-
Specific adaptive immune responses are then activat-
talia of their infants has been well-documented. 8
ed, principally by cytotoxic T-cells, auxiliary T cells
HPV transmission through close contact with their
and antibodies that neutralize the virus, preventing
carers has also been reported. Due to the possibility
reinfection and dissemination in extracellular phases.
that children with external genital warts may have
The complement also exerts activity on viral infec-
been sexually abused, communication with the rele-
tions. Toll-like receptors (TLR), which are involved in
vant child protection agency is indicated if there is a
recognizing the viral pathogen-associated molecular
strong suspicion of abuse based on the patient’s his-
patterns (PAMPs) such as TLR 2-4, 7-9, are also
Treatment of lesions resulting from HPV should
The persistence of HPV-induced lesions is prin-
be individualized. Various sessions with different ther-
cipally a consequence of defective immunosurveil-
apeutic modalities may be required to achieve com-
lance. 1 Modulation of the immune response by sys-
plete regression of the lesions. The conventional treat-
temic, topical or intralesional medication represents
ment consists of chemical destruction of the lesion by
an alternative treatment for viral infections. The effi-
topical application of podophyllin, 5-fluorouracil, bi-
cacy of this modulation is based on the regression of
FIGURE 3: Case 1. Total regression of the lesions after three weeks FIGURE 4: Case 2. Total regression of the lesions after four weeks An Bras Dermatol. 2009;84(5):549-53.Brandt HRC, Fernandes JD, Patriota RCR, Criado PR, Belda W Jr
verrucous lesions resulting from the development of
quantity applied. Systemic symptoms are rare; howev-
er, patients may present fatigue, fever, myalgia, alter-
Imiquimod is a synthetic immunomodulator for
ations to the central and peripheral nervous system and
topical use. It is an aminoquinoline compound and
exerts an effect on the cellular innate immune system
Lesions located in the mucosa are more respon-
mediated by interferon alpha and tumor necrosis fac-
sive to treatment, possibly due to better absorption. 13
tor-alpha. There is also an increase in innate and
The efficacy of treatment may be greater if imiquimod is
acquired immunity through stimulation of the toll-like
used more frequently or in combination with topical sal-
receptors of the antigen-presenting cells. Activation
icylic acid or retinoic acid. In refractory cases, imiquimod
of the immune mediators appears to be responsible
may be applied under an occlusive dressing. 13
for eradicating the HPV virus. Imiquimod induces the
The application of imiquimod has proven bene-
production of interferon-alpha (IFN-a) by the ker-
ficial for the treatment of condyloma in adults.
atinocytes, as well as other cytokines that inhibit viral
Nevertheless, its use in children is yet to be estab-
replication. Imiquimod also acts on cell immunity by
lished. The principal advantage for children is the
activating Langerhans cells, thus increasing the pres-
convenience of home treatment and the absence of
entation of antigens for the T-cells. 1,11,13
pain. The number of cases in which local irritation led
Imiquimod treatment of lesions resulting from a
to discontinuation of treatment is minimal, and care-
viral infection such as condyloma acuminatum in adults
ful application, avoiding contact with normal skin or
and viral warts and mollusca contagiosa in children has
decreasing the frequency of use, minimizes this risk.
Complete regression of condyloma was report-
lesions is achieved in 72-84% of cases, local recurrence
ed in children of 6 and 19 months following applica-
rates ranging from 5 to 19%. The advantage of this
tion of imiquimod for 3 and 8 weeks, respectively. 11,15
treatment for children is the convenience of a treat-
Despite the frequent observation of perilesional ery-
ment that can be applied painlessly in the home, which
thema, no significant side effects were found in the
is not the case with many of the ablative therapies. 11,12
cases reported or in the cases presented here.
Imiquimod 5% cream is well tolerated, the most com-
The observation of these four successfully treat-
mon adverse events being erythema, burning, erosion
ed cases of genital warts in childhood suggests that
and hypersensitivity, which are usually limited to the
imiquimod 5% cream is a safe, effective alternative
site of application. Systemic absorption of imiquimod
therapy that should be considered as an option to
is less than 1% of the total amount applied topically and
aggressive painful treatments and also to surgical
is more associated with the surface area than with the
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MAILING ADDRESS / ENDEREÇO PARA CORRESPONDÊNCIA:
et al. Cancer associated human papilomavirus:
perinatal transmission and persistence. Br J Obstet
Av. Dr. Enéas Carvalho de Aguiar, 255 - 3º andarDivisão de Clínica Dermatológica - ICHC
Gutman LT, St Claire K, Herman-Giddens ME, Johnston
WW, Phelps WC. Evaluation of sexually abused and
Tel.fax: +55 11 3069 8002; +55 11 3088 9145
nonabused young girls for intravaginal human
How to cite this article/Como citar este artigo: Brandt HRC, Fernandes JD, Patriota RCR, Criado PR, BeldaW Jr. Treatment of human papillomavirus in childhood with imiquimod 5% cream. An Bras Dermatol. 2010;85(4):549-53. An Bras Dermatol. 2010;85(4):549-53.
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