Infant’s diaper hides anogenital lesions

Child with nonerythematous papules on the thigh and genital area.

The Case

You are asked to evaluate a healthy 6-month-old boy who has had 5 nonerythematous papules in the right groin area for 2 months. The parents have treated the papules with a salicylic acid compound with no results. The papules do not seem to be pruritic because the boy does not appear bothered by them.

DERMCASE diagnosis: ANOGENITAL WARTS

Epidemiology

Of the 30 to 40 variants of human papillomavirus (HPV) that affect the genital tract,¹ HPV 6 and HPV 11 are most commonly associated with the development of anogenital warts. Although sexual abuse should be evaluated in every case of pediatric genital warts, the majority of anogenital warts in infants and children aged younger than 3 years are acquired nonsexually.

Sexual transmission

Sexually abused children have been reported to have a prevalence of 3.4% to 33% HPV DNA and/or abnormal pap cytology and a 0.3% to 2% prevalence of genital warts.^2,3 The positive predictive value of the presence of external genital warts for sexual abuse was 37% for children aged 2 to 12 years and increased with age.⁴ However, in many of these studies there may be a significant reporting bias. Evaluation is difficult because many sexually abused children will not harbor the virus or have evidence of physical trauma.^5,6 Moreover, children with abnormal genital findings may not have been sexually abused. Although the average time from exposure to development of warts is 3 months, the incubation period may be up to 5 years.^4,7

Perinatal transmission

Perinatal transmission occurs from direct contact with an infected maternal genital tract during delivery.⁸ The risk of perinatal transmission is at most 2.8%.⁹ In pregnant women with cervical dysplasia, HPV DNA was detected in amniotic fluid obtained by transabdominal amniocentesis prior to membrane rupture.¹⁰ Reports of anogenital warts in infants at birth suggest the possibility of hematogenous transmission.¹¹ Alternatively, the findings may be explained by ascending infection via microscopic tears in the placental membranes. Other investigators have suggested that latent perinatal infection may develop in some neonates with clinical expression delayed for up to 5 years.⁴

Autoinoculation or heteroinoculation

Autoinoculation or heteroinoculation from nongenital warts may lead to the development of anogenital warts in children. Human papillomavirus types 1, 2, 27, and 57 are most commonly associated with hand warts¹² and have been reported in non–sexually transmitted anogenital lesions.¹³ These HPV subtypes do not show high degrees of site specificity as is seen in adults.¹⁴ Although HPV DNA has been detected in finger brush samples of adults with genital HPV, which could potentially be transferred to their children by finger-genital contact,¹⁵ it is unclear whether the presence of HPV DNA itself is capable of inducing active infection without abrasion of the skin.

Fomites

Seventy-five percent of virginal girl relatives of adults with anogenital warts showed subclinical lesions.¹⁶ However, the presence of HPV DNA does not indicate clinical disease. Although transmission by fomites is suggested by several studies, the relationship to development of clinical infection is unclear.

Diagnosis and treatment

The differential diagnosis in infants and young children includes molluscum, pyramidal protrusion, and eczema. In older children and adolescents, pearly penile papules and micropapillomatosis also should be considered. Rarely, biopsy may be indicated. Differential diagnoses such as micropapillomatosis labialis in girls or pearly penile papules in boys and other sexually transmitted infections such as Chlamydia trachomatis should be ruled out. Biopsy may be indicated for atypical or persistent lesions (such as bowenoid papulosis and giant condylomas).¹⁷

Management should include a thorough history and physical examination of the child for warts and signs of physical injury and the potential referral of family members for examination. Suspected sexual abuse cases should be reported to child protective services, and studies to exclude other sexually transmitted diseases should be submitted. However, because most cases of anogenital warts in infants and young children are acquired nonsexually, nonjudgmental evaluation is important, and counseling regarding lack of symptoms in many children and the high rate of regression without treatment should be reassuring.

HPV genotyping

Evidence shows that performing HPV DNA typing in children and adolescents is not recommended for the following reasons. Often HPV infections are asymptomatic and transient, and are eliminated by a healthy immune system, similar to common warts. Because the virus does not display a strong degree of tropism, viral subtype cannot determine mode of transmission.⁸ Human papillomavirus has low sequence variability and may not vary between hosts without any direct contact. The presence of HPV DNA without clinical disease does not indicate effective treatment.¹⁸

Although not approved for use in children, imiquimod or podophyllotoxin may be used safely and effectively in infants and young children for symptomatic lesions. However, careful titration of these agents is important to minimize the risk of irritation.

Children infected with HPV 16 or HPV 18 should have lifelong evaluation to prevent cervical, vaginal, vulvar, penile, oropharyngeal, or anal cancer.¹⁹

Our patient

Evaluation of our patient revealed no evidence of sexual or physical abuse. Because the lesions were not symptomatic, the family elected to postpone treatment at this time.

REFERENCES

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2. Moscicki AB. Genital infections with human papillomavirus (HPV). Pediatr Infect Dis J. 1998;17(7):651-652.

3. Gibbs NF. Anogenital papillomavirus infections in children. Curr Opin Pediatr. 
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lessons from a decade of research. Pediatrics. 1999;104(1 pt 2):178-186.

6. Berenson AB, Chacko MR, Wiemann CM, Mishaw CO, Friedrich WN, Grady JJ. A case-control study of 
anatomic changes resulting from sexual abuse. Am J Obstet Gynecol. 2000;182(4):820-831.

7. Oriel JD. Natural history of genital warts. Br J Vener Dis. 1971;47(1):1-13.

8. Jayasinghe Y, Garland SM. Genital warts in children: what do they mean? Arch Dis Child. 2006:91(8):696-700.

9. Watts DH, Koutsky LA, Holmes KK, et al. Low risk of perinatal transmission of human papillomavirus: results from a prospective cohort study. Am J Obstet Gynecol. 1998;178(2):365-373.

10. Armbruster-Moraes E, Ioshimoto LM, Leão E, Zugaib M. Presence of human papillomavirus DNA in amniotic fluids of pregnant women with cervical lesions. Gynecol Oncol. 1994;54(2):152-158.

11. Tang CK, Shermeta DW, Wood C. Congenital condylomata acuminata. Am J Obstet Gynecol. 1978;131(8):912-913.

12. de Villiers EM. Human pathogenic papillomavirus types: an update. Curr Top Microbiol Immunol. 1994;186:1-12.

13. Hammerschlag MR. Sexually transmitted diseases in sexually abused children: medical and legal implications. Sex Transm Infect. 1998;74(3):167-174.

14. Armstrong DK, Handley JM. Anogenital warts in prepubertal children: 
pathogenesis, HPV typing and management. Int J STD AIDS. 1997;8(2):78-81.

15. Bosch FX, Iftner T. The aetiology of cervical cancer. NHSCSP Publication No. 22. Sheffield, UK: NHS Cancer Screening Programmes; 2005.

16. Pacheco BP, Di Paola G, Ribas JM, Vighi S, Rueda NG. Vulvar infection caused by human papillomavirus in children and adolescents without sexual contact. J Pediatr Adolesc Gynecol. 1991;4(3):136-142.

17. von Krogh G, Lacey CJ, Gross G, Barrasso R, Schneider A. European course on HPV associated pathology: guidelines for primary care physicians for the diagnosis and management of anogenital warts. Sex Transm Infect. 2000;76(3):162-168.

18. Winer RL, Kiviat NB, Hughes JP, et al. Development and duration of human papillomavirus lesions, after initial infection. J Infect Dis. 2005;191(5):731-738.

19. Watson M, Saraiya M, Ahmed F, et al. Using population-based cancer registry data to assess the burden of human papillomavirus-associated cancers in the United States: overview of methods. Cancer. 2008;113(10 suppl):2841-2854.

Ms Kuwabara is a third-year medical student, Johns Hopkins University School of Medicine, Baltimore, Maryland. Dr Cohen, section editor for Dermcase, is professor of pediatrics and dermatology, Johns Hopkins University School of Medicine, Baltimore. The author and section editor have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article. Vignettes are based on real cases that have been modified to allow the author and section editor to focus on key teaching points. Images also may be edited or substituted for teaching purposes.