Possible modes of transmission of human papilloma virus (HPV) in children include perinatal transmission, sexual transmission or extragenital contact. Conventional treatment options with chemical and physical destruction methods can be difficult and painful and often require general anesthesia. Imiquimod is topically active immunomodulatory agent and it\u27s use for pediatric anogenital warts has been reported with good results. We report a case of extensive anogenital warts in a 18-months-old girl who was successfully treated with topical 5% imiquimod cream.</p

Nives Pustišek

Nives Šikanić Dugić

Suzana Ljubojević

Vlasta Hiršl Hećej

English

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40 ACTA DERMATOVENEROLOGICA CROATICATreatment of Anogenital Warts in an 18-month-old Girl with 5% Imiquimod CreamNives Šikanić Dugić¹, Suzana Ljubojević Hadžavdić², Nives Pustišek¹, Vlasta Hiršl Hećej¹¹Department of Reproductive Health, Children’s Hospital Zagreb; ²Zagreb University Hospital Centre, Department of Dermatology and Venerology, School of Medicine University of Zagreb, Zagreb, CroatiaCorresponding author: Nives Šikanić Dugić, MD, MSDepartment of Reproductive HealthChildren’s Hospital ZagrebKlaićeva 1610000 ZagrebCroatianives.sikanicdugic@kdb.hrReceived: February 7, 2013Accepted: November 27, 2013Acta Dermatovenerol Croat                     2014;22(1):40-43                              CASE REPORTSUMMARY Possible modes of transmission of the human papilloma virus (HPV) in children include perinatal transmission, sexual transmission, or extragenital contact. Conventional treatment options with chemical and physical destruction methods can be difficult and painful and often require general anesthesia. Imiquimod is a topically active immunomodulatory agent that has been shown to successfully treat pediatric anogenital warts. We report on a case of extensive anogenital warts in a 18-month-old girl who was successfully treated with topical 5% imiquimod cream.KeY WoRdS: anogenital warts, children, imiquimodInTRodUCTIon  Condyloma acuminatum, i.e. genital warts, are caused by infection with the human papilloma virus (HPV), mostly by low risk HPV 6 and 11. The incidence of anogenital warts in children is unknown but is suspected to be on the rise based on the increase in adult HPV infections (1). Perinatal infection may occur transplacentally via amniotic fluid during gestation and delivery, and through direct exposure to cervical and genital lesions during birth. In addition to sexual abuse, postnatal infections can be acquired through heteroinoculation or autoinoculation from nongeni-tal mucocutaneous HPV sources and fomite transmis-sion (2). Several studies have demonstrated that HPV can be acquired in the neonatal period, persisting in some infants for up to 26 months (3). Surgical treat-ment options include cryotherapy, laser vaporisa-tion, electrocautery, and excision. These methods are painful, often requiring general anesthesia. with re-currences being common. Nonsurgical approaches in children include the use of podophyllotoxin and im-iquimod. Although some studies demonstrate their safety and efficacy, these drugs are not approved for use in children under 12 years of age (1,4).We report on a 18-month-girl with extensive ano-genital warts who was successfully treated with topi-cal 5% imiquimod cream. CASe RepoRTA healthy 18-month-old female child was referred to our Department of pediatric and adolescent gyne-cology, Children’s Hospital Zagreb, with a 7-month history of anogenital warts. The girl was born by Cae-sarean section because of pelvic presentation. She 41ACTA DERMATOVENEROLOGICA CROATICAŠikanić Dugić et al. Acta Dermatovenerol CroatImiquimod in children’s anogenital warts 2014;22(1):40-43was a healthy child until the warts started to grow. She was previously unsuccessfully treated with 5-fluorouracil cream, fluorouracil and salicylic acid solu-tion, 50% and 80% trichloracetic acid, as well as cryo-therapy in another institution. The father reported genital warts 5-months ago, when he was treated by cryotherapy. He was evaluated by our dermatologist, and had no evidence of genital warts at the time. The mother was also evaluated, but no symptoms of HPV infection were found, and she had no history of geni-tal warts. Physical examination of the child was normal ex-cept for the presence of multiple skin-colored, conflu-ent verrucous papules affecting the vulva and peri-anal region (Figure 1). Gynecological examination showed no abnormalities. The hymen was intact, and there was no evidence of ulcerations or other signs of trauma to the vaginal or anal orifices. A biopsy of the warts was performed under local anesthesia and low risk HPV was confirmed using Digene Hybrid Capture II test. The histologic picture was typical for hyperpro-liferative papilloma, showing abundant koilocytosis and being compatible with condyloma. The girl was treated with 5% imiquimod cream, applied at home to the lesions three times a week, before bedtime. After 8 to 10 hours, the cream was removed by washing the treated area with mild soap and water. The mother and child visited our hospital every 3-4 weeks and at every visit, there was evident reduction in the number and size of warts. Treatment was continued for a total of 11 weeks, during which time the lesions cleared almost completely (Figure 2). At the end of the imiquimod treatment, the remains of three small papules fell down spontaneously 3 days later, and complete clearance of the lesions was achieved. Only one adverse effect was recorded, a one-day burning of the perilesional skin. No systemic adverse effects were noticed. After eighteen months of follow–up there was no evidence of recurrence.dISCUSSIonCondylomata acuminata are anogenital warts caused by the human papilloma virus (HPV), mostly by low risk HPV 6 and 11, but types 1, 2, 16, and 18 are also found. The highest risk population for HPV infection are sexually active young people under the age of 26, especially sexually active adolescents. Condyloma in the children under the age of 3 years is commonly believed to be vertically transmitted from a virally infected genital tract or through caretakers with hand warts (3). Although genital warts in small children may be vertically transmitted, sexual abuse must always be ruled out through social history and physical examination for signs of abuse (5,6). In our case, there was no evidence of sexual abuse on clini-cal examination, although the girl’s father had been treated for genital condyloma several months ago. In this case, the probable route of transmission is non-sexual, close contact with her father in his role as a caregiver. Diagnosis of anogenital warts is usually made on physical examination. A biopsy and HPV detection using Digene Hybrid Capture II test can also be done to detect the viral type or if the diagnosis is question-Figure1. Multiple skin-colored, confluent verrucous papules in the vulvar and perianal regions, prior to treatment.Figure 2. Total regression of lesions after 11 weeks of imiquimod treatment.42 ACTA DERMATOVENEROLOGICA CROATICApublication yearAuthors Faculty Age Sex Area duration oftherapyoutcome Side effects  no recurrence2001 Gruber and WilkinsonUK 2 years Boy Perianal 5 weeks Cleared Mild pruritus 15 months2001 Moresi et al. USA <2 years (n=2) 2-5 years(n=3) >5 years(n=3)   Four boys Four girlsPerianal:  eight Genital lesions: one Boy and one girl2 months for four.3-4 months for fourCleared in sixRemained in twoFew or none in fourItching in oneRedness in oneIrritation in two6-12 months in  six patients2001 Schaen and MercurioUSA 6 months Girl Perianal + vulvar3 weeks Cleared None No date2003 Mayewski et al.Poland 19 months Boy Perianal 8 weeks Cleared Local erythema 6 months2007 Campaner et al.Brazil 7 years Girl Perianal + vulvar12 weeks Add electrocauteryLocal erythema, burning, and itching6 months2010 Masuko Japan 28 months Girl Perianal + vulvar7 weeks Cleared None 4 weeks2010 Clivati Brand et al.Brazil 1 year2 years18 months2 yearsBoyBoyGirlGirlPerianalPerianalPerianalPerianal+ vulvar4 weeks3 weeks4 weeks3 weeksClearedClearedClearedClearedNoneLocal erythemaNoneNone6 months in all 2012 Leclair et al. Canada 3 years Girl Perianal+ groin +glutea6 weeks Cleared Minor redness 24 months2013 Our case Croatia 18 month Girl Perianal+vulvar11 weeks Cleared Mild local burning 18 monthsTable 1. The use of imiquimod 5%  cream for pediatric anogenital warts. Modified table from Masuko et al (8).able, or when child abuse is suspected. In our patient, we have did both diagnostic tests which established the diagnosis of condylomata acuminata.Treatment of lesions resulting from HPV should be individualized. The conventional therapy treat-ment includes chemical and physical destruction of the lesions. They often require the use of anesthesia, and recurrences of the lesions are common (7). Our patient was treated with most of the conventional methods, but without any result.Imiquimod is a topically active immunomodula-tory agent that induces keratinocytes to produce in-terferon alfa and other cytokines in order to inhibit viral replication. Imiquimod also enhances cell-me-diated immunity (8). The use of imiquimod for pe-diatric anogenital warts has been reported to be an effective treatment (7,9-11,14). An overview of these results was presented by Masuko et al. (8). We have modified their table with new cases (Table 1). In these studies, duration of treatment was between 2 and 12 weeks. Duration of therapy in our case was 11 weeks, and the rest of three small papules resolved sponta-neously three days after the therapy with imiquimod was finished. Complete clearance of the lesions was achieved. Imiquimod treatment has been shown to be a successful treatment for condylomata acuminata in adults and long-lasting cutaneous warts and mol-luscum contagiosum in children. Clearance of exter-nal warts is achieved in 72% to 84% of the cases, and local recurrence rates were 5%-19% (12). In case of incomplete resolution, some authors suggest that a combination of imiquimod and destructive methods may play a role in the treatment of extensive condy-loma (12).Overall, 5% imiquimod cream is well tolerated. The most common adverse reactions include erythema, burning, itching, and tenderness, frequently limited to application sites. Less than 1% of the cream ap-plied topically is absorbed systematically. Side effects are usually mild and well-tolerated (13). Although the treatment in our case lasted 11 weeks, only mild one-day burning was present.ConClUSIon Therapy with immiquimod has many advantages, such as easy, painless application at home, mild side effects, and a low recurrence rate. It is safe and toler-able in children. Disadvantages include the high price Šikanić Dugić et al. Acta Dermatovenerol CroatImiquimod in children’s anogenital warts 2014;22(1):40-4343ACTA DERMATOVENEROLOGICA CROATICAof the cream, especially in long term application. Im-miquimod could be the first line of treatment for ex-tensive condyloma in children. Despite the excellent response to imiquimod, careful long-term follow-up is indicated because of the risk of recurrences and un-known risk of development of anogenital neoplasia.References1. Sinclair KA, Woods CR, Sinal SH. Venereal warts in children. Pediatr Rev 2011;32:115-21.2. Sinclair KA, Woods CR, Kirse DJ, Sinal SH. Anoge-nital and respiratory tract human papillomavirus infections among children: age, gender and po-tential transmission through sexual abuse. Pedia-trics 2005;116:815-25.3. LaCour DE, Trimble C. Human papillomavirus in infants: transmission, prevalence and persistence. J Pediatr Adolesc Gynecol 2012;25:93-7.4. Thornsberry L, English JC 3rd. Evidence-based tre-atment and prevention of external genital warts in female pediatric and adolescent patients. J Pe-diatr Adolesc Gynecol 2012;25:150-4.5. Silverberg N. Human papillomavirus infections in children. Curr Opin Pediatr 2004;16:402-9.6. Woods CR. Sexually transmitted diseases in pre-pubertal children: mechanisms of transmission, evaluation of sexually abused children and ex-clusion of chronic perinatal viral infection. Semin Pediatr Infect Dis 2005;16:317-25.7.  Brandt HRC, Fernandes JD, Patriota RCR, Criado PR, Belda WJr. Treatment of human papillomavi-rus in childhood with imiquimod 5 % cream. An Bras Dermatol 2010;85:549-53.8.  Masuko T, Fuchigami T, Inadomi T, Inamo Y, Hashi-moto K. Effectiveness of imiquimod 5% cream for treatment of perianal warts in a 28-month-old child. Pediatr Int 2011;53:764-6.9.  Guber PC, Wilkinsom J. Succesful treatment of pe-rianal warts in a child with 5% imiquimod cream. J Dermatolog Treat 2001;12:215-7.10. Schaen L, Mercurio MG. Treatment of human pa-piloma virus in a 6-month-old infant with imiqui-mod 5 % cream. Ped Dermatol 2001;18:450-2. 11. Majewski S, Pniewski T, Malejczyk M, Jablonska S. Imiquimod is highly effective for extensive, hy-perproliferative condyloma in children. Pediatr Dematol 2003;20:440-2.12. Campaner AB, Santos RE, Longo Galvao MA, Beznos GW, Aoki T. Effectiveness of imiquimod 5% cream for treatment of extensive anogenital warts in seven-year-old child. Pediatr Infect Dis J 2007;26:265-6.13. Cullton DA, Morrell DS, Burkhart CN. The mana-gement of condyloma acuminata in the pediatric population. Pediatr Ann 2009;38:368-72.14. Leclair E, Black A, Fleming N. Imiquimod 5% cream treatment for rapidly progressive genital condylo-ma in a 3-years-old girl. J Pediatr Adolesc Gynecol 2012;25:119-21.Šikanić Dugić et al. Acta Dermatovenerol CroatImiquimod in children’s anogenital warts 2014;22(1):40-43

Treatment of Anogenital Warts in an 18-month-old Girl with 5% Imiquimod Cream

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