NASPAG Clinical Recommendations Clinical Recommendation: Labial Adhesions Janice L. Bacon MD 1, Mary E. Romano MD, MPH 2,*, Elisabeth H. Quint MD 3 1 2 3
Department of Obstetrics and Gynecology, University of South Carolina School of Medicine, Columbia, South Carolina Department of Pediatrics, Division of Adolescent Medicine, Children's Hospital at Vanderbilt, Nashville, Tennessee Department of Obstetrics and Gynecology, C.S. Mott Children's Hospital, University of Michigan Health System, Ann Arbor, Michigan
a b s t r a c t Labial adhesions, also known as labial agglutination, are a common finding in prepubertal adolescents. They are defined as fusion of the labia minora in the midline or are termed vulvar adhesions when they occur below the labia minora (inner labia). Patients are often asymptomatic but might present with genitourinary complaints. The decision for treatment is based on symptoms. The mainstay of treatment in asymptomatic patients is conservative, with careful attention to vulvar hygiene and reassurance to parents. In symptomatic patients, topical treatment with estrogen and/or steroid cream is often curative. Less often, corrective surgery is necessary. Recurrence is common until a patient goes through puberty. These recommendations are intended for pediatric and gynecologic health care providers who care for pediatric and adolescent girls to facilitate diagnosis and treatment. Key Words: Labial adhesions, Labial agglutination, Labial fusion, Vulvovaginitis, Vulvovaginal disorders, Pediatric gynecology
Epidemiology
Labial adhesions are presumed to be an acquired condition. They occur most commonly between 3 months and 3 years of age. The estimated prevalence of labial adhesions is 0.6%-5% with a peak incidence between 13 and 23 months of age. One study reported a peak incidence of 3.3% in this age group.1 Labial adhesions commonly occur in the absence of any other upper genital tract pathology. There are isolated case reports of labial adhesions in adolescents, adults, and older women as a result of estrogen deficiency, like menopause. Vulvovaginal inflammation, Steven Johnson syndrome, lichen sclerosis, and graft vs host disease, can result in a similar predisposition toward adhesion formation.2 Other predisposing conditions include Behcet disease, female circumcision, and trauma secondary to sexual abuse.2 Pathophysiology
The development of labial adhesions is thought to be caused by vulvar inflammation in a low-estrogen environment. This is supported by the fact that labial adhesions are uncommon in the immediate newborn period and during The authors indicate no conflicts of interest. This Clinical Recommendation was prepared by Janice Bacon, MD, and Mary Romano, MD, MPH, with expert review from Elisabeth Quint, MD. This document has been reviewed by the Education Committee and approved by the Board of the North American Society of Pediatric and Adolescent Gynecology. This Clinical Recommendation reflects the currently available best evidence for practice at the time of publication. This recommendation is designed to aid practitioners is making decisions about appropriate care, but should not be construed as dictating an exclusive course of management. Variations in practice might be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice. * Address correspondence to: Mary E. Romano, MD, MPH, Department of Pediatrics, Division of Adolescent Medicine, Children's Hospital at Vanderbilt, 719 Thompson La Ste 36300, Nashville, TN 37204; Phone: (615) 830-4680 E-mail address: [email protected] (M.E. Romano).
the reproductive years when estrogen levels are highest. There have been isolated case reports of patients with premature thelarche (breast development) and labial adhesions, which would support a multifactorial etiology for labial adhesion formation.3 Inflammation from infection or trauma can erode the epithelium of the labia minora, which, in the absence of estrogen might fuse in the midline. Inflammation might occur as a result of poor perineal hygiene. Stool contamination of the vulva may produce vulvovaginitis and contribute to inflammation. Attention to hygiene may be sufficient for resolution of the adhesions.4 There are certain inflammatory conditions with which labial adhesions have been associated. Lichen sclerosis is associated with labial adhesions as a result of ongoing disease-mediated inflammation. Adhesions typically develop in older patients and are more anterior in location. In a review of the literature, the typical age range for patients with adhesions attributed to lichen sclerosis was between 2 and 10 years of age.1 In patients known to have vulvar dermatoses, careful and regular inspection of the external genitalia is recommended to monitor for the development of labial adhesions. If labial adhesions are found in this subset of patients, referral to a gynecologic provider is recommended. Candidal vulvovaginitis in patients with poorly controlled diabetes mellitus, recent antibiotic use, or in infants with frequent diaper rashes can also be a contributing factor.5 Other infectious etiologies predispose to adhesionsdmost commonly group A Streptococcus after a vulvovaginal skin infection. Although vaginal infection with Neisseria gonorrhea, Gardnerella vaginalis, Chlamydia trachomata, or Trichomona vaginalis in children are less common, they can be etiologies of chronic vulvar inflammation and labial adhesions.5 Any sexually transmitted infection in this population necessitates consideration of sexual abuse.5
1083-3188/$ - see front matter Ó 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jpag.2015.04.010
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Table 1 Pathophysiology of Labial Adhesions Poor perineal hygiene Trauma Straddle injury Female circumcision Sexual abuse Excessive perineal cleaning Infection Candida Group A Streptococcus Neisseria gonorrhea Gardnerella vaginalis Chlamydia trachomata Trichomona vaginalis Vulvar dermatoses Lichen sclerosis Mechanical factors Diaper use
Genital trauma can also lead to labial adhesions. This can be the result of female circumcision or a straddle-like injury. Labial adhesions have been documented in patients with a history of sexual abuse.6 Multiple studies have attempted to document the genital examination findings in patients with suspected sexual abuse. However, it has been difficult to establish a reliable consensus on physical examination findings in this setting.6 Partial labial adhesions was reported in a case control study as a statistically significant physical finding among Caucasian patients with a reported history of abuse.6 Other patient populations demonstrated no difference between abuse patients and control participants. The most common finding in this study was vaginal discharge.6 In evaluation of a patient with labial adhesions it is important for every provider to ask about the possibility of sexual abuse and exclude this as the cause for labial adhesions. Finally, labial adhesions have also been attributed to mechanical factors. Adhesions are uncommon after 6 years of age although for most girls puberty and an increase in estrogen production do not occur for many years.2 Physical apposition of the labia minora in diaper-wearing girls is thought to facilitate the development of adhesions in some cases. Decreased diaper use and increased ambulation allow for more physiologic separation of the labia minora, which reduces the possibility of adhesions (Table 1).7
A
Clinical Presentation and Diagnosis
Labial adhesions are often asymptomatic and diagnosed in a routine genital examination (Fig. 1A). When symptomatic, patients with adhesions may present with abnormal voiding, postvoid urinary dribbling, vaginal pain or discharge, and urinary tract infections. Among patients with labial adhesions, the prevalence of symptoms is not consistently reported. A 2009 retrospective study investigated 151 patients (ages 0.25 to 8.75 years) with labial adhesions. In those patients symptoms were reported as follows: 7.3% with urinary frequency, 19.9% with urinary tract infections (confirmed with positive urine culture), 8.6% with vaginitis, and 12.6% with postvoid dripping. Approximately 50% of patients were asymptomatic.2 The diagnosis is made using close clinical inspection. The degree of adhesions can range from the entire length of the labia minora to only a small portion. There is a midline area of clear, fibrotic tissue (which appears gray) at the site of adhesion, referred to as the raphe. Partial adhesions more commonly occur posteriorly and may completely occlude the vaginal opening. In these patients, absence of the vagina and an imperforate hymen must be excluded. Close inspection and identification of the absence of hymeneal tissues (which is covered by the adhesions) and a midline raphe can help to distinguish labial adhesions from absence of the vagina.8 Rarely, with more extensive adhesions there might be complete blockage of the urogenital opening, including the urethra.8 Although underlying pathology is often not determined in patients with labial adhesions, patients with additional or atypical findings (older age, anterior location, signs of systemic medical disorders and/or dermatological conditions) at presentation require further workup and evaluation. Symptoms suggestive of infection (dysuria, vaginal discharge, or erythema) should prompt an evaluation for underlying infection with urine and/or vaginal cultures. Treatment Observation
Currently, conservative management is considered the most appropriate approach.9,10 In asymptomatic patients with labial adhesions without urinary retention or
B
Fig. 1. (A) Gentle labial traction to evaluate and confirm labial agglutination. This same traction assists separation during the application of topical medications. (B) A cotton-tipped applicator can also be used to assist with gentle separation.
J.L. Bacon et al. / J Pediatr Adolesc Gynecol xxx (2015) 1e5
infection, observation without intervention should be considered. Most patients will have spontaneous resolution of the adhesions when endogenous estrogen production begins. Resolution without therapy has been noted to be as high as 80% within 1 year.11 Refraining from active intervention might be most appropriate in asymptomatic girls who wear diapers, because this group has the highest rate of recurrence. A study by Leung et al (35 girls, 13-23 months of age) showed a recurrence rate of 41% in patients followed 2-72 months after treatment of any kind.12 Estrogens
Traditionally, the treatment for labial adhesions has been use of topical estrogens, with or without manual separation in the office setting.9 When therapy is appropriate, topical estrogen preparations, such as conjugated estrogen vaginal cream (Premarin Vaginal Cream; Pfizer) or estradiol (0.01%) vaginal cream (Estrace Vaginal Cream, USP, 0.01%; Warner Chilcott) remain the first-line medical treatment. Estradiol vaginal cream contains 0.1 mg estradiol in a nonliquifying base composed of water, propylenegylcol, and other compounds, and lacks alcohols that might cause the burning or discomfort of some other preparations. The application of topical estrogen is most appropriate when applied in scant amounts to the midline raphe.8,13 Application might be by fingertip or Q-tip, once or twice a day. Gentle traction, during application of the cream, increases the rate of separation of the adhesions (Fig. 1A). The duration of therapy has varied in studies ranging most commonly from 2 to 6 weeks. A direct relationship between the length of therapy and resolution of adhesions has not been shown. The most common side effects of topical estrogen use include irritation, redness, breast budding, and hyperpigmentation of the vulva. These complications might be minimized with time-limited and appropriate application to avoid unnecessary systemic absorption of estrogen. Rarely, scant vaginal bleeding from stimulation of the endometrium and subsequent shedding have been reported. These side effects are transient and usually resolve after use of the preparation has been discontinued.12,14 Monitoring of breast bud resolution after therapy discontinuation is recommended.8 Resolution of labial adhesions with topical estrogen is reported to be as high as 50%-89%. Success rates also appear to be the highest in female patients with a thin, translucent raphe.10,14,15 Variable results in the literature might reflect the composition and the size of the study groups, suspected duration and thickness of the adhesions, history of recurrence, and previous therapy success. Steroids
Topical betamethasone 0.05% is an alternative for the management of labial adhesions. The basis for the original consideration of this medication was a high rate of success as a nonsurgical method of managing phimosis in young boys.16 Twice daily application combined with gentle traction was successful in 67%-95% of
3
boys.16 An initial small sample of girls with labial adhesions treated with topical 0.05% betamethasone as a therapy for recurrent adhesions or for patients in whom treatment with topical estrogen cream had failed, obtained 68% success in resolution of the adhesions after twice daily application to the raphe for 4-6 weeks.17 Even when topical betamethasone 0.05% was used for up to 3 treatment courses, researchers noted enhanced resolution of the labial adhesions without side effects.18 Another retrospective study suggested that application of 0.05% betamethasone resulted in earlier resolution of labial adhesions with less recurrence compared with topical estrogen therapy.2 Short-term side effects of betamethasone include erythema, pruritus, and folliculitis, skin atrophy, or fine hair growth. Manual Separation
Adhesions of rapid onset, those accompanied by severe symptoms such as urinary retention, adhesions for which medical therapy has failed, or those that appear thick without a visible transparent raphe might be primarily or secondarily treated with manual separation. If the treating provider is uncomfortable or inexperienced with manual separation techniques, a referral to a physician or provider with expertise in pediatric and adolescent gynecology might be considered. Manual separation performed by pulling the labia apart without topical anesthetic or sedation is unnecessarily painful and potentially traumatic for the child and therefore this technique should not be performed. Recurrent forceful separation might result histologically in thicker, more resistant adhesions hypothesized to be associated with bleeding, inflammation, fibrosis, and a potential for increased rates of recurrence.17,18 Surgical separation is best performed using application of a topical anesthetic. Approximately 5-10 minutes after application of lidocaine ointment 2% or 5% or 30 minutes after application of EMLA (a topical prilocaine 2.5%/lidocaine 2.5% combination; APP Pharmaceuticals) the separation can be attempted. The product insert for prilocaine/lidocaine contains recommended dosing for children based on age and weight in kilograms. Medical sedation in an outpatient setting or operating room might be considered for patients unable to tolerate an office procedure.19,20 No specific technique of surgical separation has been studied, nor do most studies provide details of the methods used, but textbooks describe use of a lubricated Q-tip inserted into the opening in the adhesions and pulled along the raphe (see Fig. 1B). Making the initial separation with a sharp blade and gently pulling a Q-tip or probe forward has been mentioned. These gentle techniques attempt to minimize tissue trauma and therefore recurrent adhesions. Magnification with operating loupes or a colposcope might be helpful. When separation has been accomplished, application of topical estrogen has been demonstrated to enhance epithelialization and healing. Topical treatment with estrogen is recommended for several weeks, once or twice daily. The frequency of application and duration of postoperative therapy has not been specifically studied, but 2-4 weeks is most commonly cited.21 After this time, attention to perineal cleaning and application of a bland emollient for
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Table 2 Labial Adhesions: Management Options Asymptomatic Patients Symptomatic patients (mild)
Symptomatic patients (moderate/severe; nonresponse to medical therapy)
Conservative Therapy. Optimize Vulvar Hygiene (A) Topical estrogen, 1 to 2 times daily for 2 to 6 weeks (B) Topical steroids. May use as first-line therapy or as an adjuvant to topical estrogen. May also use if treatment with topical estrogen fails. One to 2 times daily for 4 to 6 weeks Referral to a specialist for manual separation Manual separation should be performed with topical anesthetic with or without adjunctive sedation To limit recurrence of adhesions, topical estrogen should be used followed by extended use of bland emollients
several months has also been recommended, although the exact duration to best decrease recurrence of labial adhesions has not been defined (Table 2).8,9,14
separation using topical anesthesia with or without adjunctive sedation. Level C
Recurrence III
The reported incidence of recurrent labial adhesions varies widelyd7%-55% in a case series. Because of the high rates of recurrence, parents should be informed about the possibility of recurrence during the course of treatment. Risks for recurrent adhesions decrease with increasing age, and are lowest after production of endogenous estrogen begins.2,11,17,18,22,23 Patients prone to recurrent labial adhesions might have had thick adhesions with a less visible midline raphe. Factors that contribute to recurrent adhesions include poor perineal hygiene, vigorous cleansing techniques, trauma, recurrent genital infections, or persistent medical or dermatological disorders.9 The initial method of treatment has not been shown to be a contributing factor to recurrent disease.8,10 The management of recurrent adhesions should include the same treatment considerations used for treatment of the initial adhesions: conservative therapy (optimize vulvar hygiene) with observation and topical estrogen or betamethasone 0.05% with repeat manual separation if needed.8,10,17 Management of recurrent adhesions has been less well studied than treatment of initial adhesions. One retrospective study showed that re-treatment of persistent or recurrent labial adhesions with topical estrogen therapy after detailed application instruction was successful in at least 35% of cases.24 Additional measures to improve perineal care and cleansing and management of any predisposing medical conditions should be emphasized. Recommendations Level A II-2, II-3
Conservative medical therapy without any intervention is recommended in asymptomatic patients. In these patients emphasis should be placed on optimizing vulvar hygiene. In symptomatic patients, short-term treatment with topical estrogen is the best initial therapeutic recommendation. Betamethasone 0.05% is an alternative or adjunctive medical therapy. II-2
Acute onset of adhesions, severe symptoms of urinary retention, recurrent infections, or adhesions not responsive to medical therapy, might be managed with manual
Prevention of recurrent adhesions includes proper genital hygiene, treatment of contributing factors, and postsurgical therapy initially with topical estrogen followed by bland emollients for an extended period of time. Acknowledgment
Education Committee, North American Society of Pediatric and Adolescent Gynecology: Jennifer Dietrich, MD, MSc (co-chair); Judith Simms-Cendan, MD (co-chair); Elise Berlan, MD; Jennifer Bercaw-Pratt MD; Lisa Jacobsen, MD, MPH; Saifudden Mama, MD, MPH; Maria Rahmandar, MD; Amy Sass, MD; Hina Talib, MD; and Andrea Zuckerman, MD. References 1. Gibbon K, Bewley A, Salisbury J: Labial fusion in children: a presenting feature of genital Lichen Sclerosis? Pediatr Dermatol 1999; 16:388 2. Mayoglou L, Dulabon L, Martin-Alguacil N, et al: Success of treatment modalities for labial fusion: a retrospective evaluation of topical and surgical treatments. J Pediatr Adolesc Gynecol 2009; 22:247 3. Papagianni M, Stanhope R: Labial adhesions in a girl with isolated thelarche: the importance of estrogenization. J Pediatr Adolesc Gynecol 2003; 16:31 4. Eroglu E, Yip M, Oklar T, et al: How should we treat prepubertal labial adhesions? Retrospective comparison of topical treatments: estrogen only, betamethasone only, and combination estrogen and betamethasone. J Pediatr Adolesc Gynecol 2011; 24:389 5. Randelovic G, Mladenovic V, Risti c L, et al: Microbiological aspects of vulvovaginitis in prepubertal girls. Eur J Pediatr 2012; 171:1203 6. Berenson A, Chacko M, Wiemann C, et al: A case- control study of anatomic changes resulting from sexual abuse. Am J Obstet Gynecol 2000; 182:820 € rk O, et al: Do hygienic factors affect labial fusion 7. Acer T, Otgun I, Oztu recurrence? A search for possible related etiologic factors. J Pediatr Surg 1913; 2012:47 8. Quint E: Labial agglutination in a teenager. J Pediatr Adolesc Gynecol 2003; 16:61 9. American College of Obstetricians and Gynecologists (ACOG): Diagnosis and management of vulvar skin disorders. Washington (DC), American College of Obstetricians and Gynecologists, 2008. 11 (ACOG practice bulletin; no. 93. 10. Schroeder B: Pro-conservative management for asymptomatic labial adhesions in the prepubertal child. J Pediatr Adolesc Gynecol 2000; 13:183 11. Pokorny S: Prepubertal vulvovaginopathies. Obstet Gynecol Clin North Am 1992; 19:39 12. Leung A, Robson W, Tay-Uycbo J: The incidence of labial fusion in children. J Paediatr Child Health 2008; 29:235 13. Van Eyk N, Allen L, Giesbrecht E, et al: Pediatric vulvovaginal disorders: a diagnostic approach and review of the literature. J Obstet Gynaecol Can 2009; 31:850 14. Starr N: Labial adhesions in childhood. J Pediatr Health Care 1996; 10:26 15. Aribarg A: Topical estrogen therapy for labial adhesions in children. Br J Obstet Gynaecol 1957; 82:424 16. Kikiros C, Beasley S, Woodward A: The response of phimosis to local steroid application. Pediatr Surg Int 1993; 8:329 17. Muram D: Treatment of prepubertal girls with labial adhesions. J Pediatr Adolesc Gynecol 1999; 12:67 18. Bacon J: Prepubertal labial adhesions: evaluation of a referral population. Am J Obstet Gynecol 2002; 187:327
J.L. Bacon et al. / J Pediatr Adolesc Gynecol xxx (2015) 1e5 19. Acker A, Jamieson MA: Use of intranasal midazolam for manual separation of labial adhesions in the office. J Pediatr Adolesc Gynecol 2013; 26:195 20. Nurzia M, Eickhorst K, Ankem M, et al: The surgical treatment of labial adhesions in pre-pubertal girls. J Pediatr Adolesc Gynecol 2003; 16:21 21. Soyer T: Topical estrogen therapy in labial adhesions in children: therapeutic or prophylactic? J Pediatr Adolesc Gynecol 2007; 20:241
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22. Nowlin P, Adams J, Nalle B: Vulvar fusion. J Urol 1949; 62:75 23. Smith C, Smith D: Office pediatric urologic procedures from a parental perspective. Urology 2000; 55:272 24. Kumetz LM, Quint EH, Fisseha S, et al: Estrogen treatment success in recurrent and persistent labial agglutination. J Pediatr Adolesc Gynecol 2006; 19:381
Department of Obstetrics and Gynecology, University of South Carolina School of Medicine, Columbia, South Carolina Department of Pediatrics, Division of Adolescent Medicine, Children's Hospital at Vanderbilt, Nashville, Tennessee Department of Obstetrics and Gynecology, C.S. Mott Children's Hospital, University of Michigan Health System, Ann Arbor, Michigan
a b s t r a c t Labial adhesions, also known as labial agglutination, are a common finding in prepubertal adolescents. They are defined as fusion of the labia minora in the midline or are termed vulvar adhesions when they occur below the labia minora (inner labia). Patients are often asymptomatic but might present with genitourinary complaints. The decision for treatment is based on symptoms. The mainstay of treatment in asymptomatic patients is conservative, with careful attention to vulvar hygiene and reassurance to parents. In symptomatic patients, topical treatment with estrogen and/or steroid cream is often curative. Less often, corrective surgery is necessary. Recurrence is common until a patient goes through puberty. These recommendations are intended for pediatric and gynecologic health care providers who care for pediatric and adolescent girls to facilitate diagnosis and treatment. Key Words: Labial adhesions, Labial agglutination, Labial fusion, Vulvovaginitis, Vulvovaginal disorders, Pediatric gynecology
Epidemiology
Labial adhesions are presumed to be an acquired condition. They occur most commonly between 3 months and 3 years of age. The estimated prevalence of labial adhesions is 0.6%-5% with a peak incidence between 13 and 23 months of age. One study reported a peak incidence of 3.3% in this age group.1 Labial adhesions commonly occur in the absence of any other upper genital tract pathology. There are isolated case reports of labial adhesions in adolescents, adults, and older women as a result of estrogen deficiency, like menopause. Vulvovaginal inflammation, Steven Johnson syndrome, lichen sclerosis, and graft vs host disease, can result in a similar predisposition toward adhesion formation.2 Other predisposing conditions include Behcet disease, female circumcision, and trauma secondary to sexual abuse.2 Pathophysiology
The development of labial adhesions is thought to be caused by vulvar inflammation in a low-estrogen environment. This is supported by the fact that labial adhesions are uncommon in the immediate newborn period and during The authors indicate no conflicts of interest. This Clinical Recommendation was prepared by Janice Bacon, MD, and Mary Romano, MD, MPH, with expert review from Elisabeth Quint, MD. This document has been reviewed by the Education Committee and approved by the Board of the North American Society of Pediatric and Adolescent Gynecology. This Clinical Recommendation reflects the currently available best evidence for practice at the time of publication. This recommendation is designed to aid practitioners is making decisions about appropriate care, but should not be construed as dictating an exclusive course of management. Variations in practice might be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice. * Address correspondence to: Mary E. Romano, MD, MPH, Department of Pediatrics, Division of Adolescent Medicine, Children's Hospital at Vanderbilt, 719 Thompson La Ste 36300, Nashville, TN 37204; Phone: (615) 830-4680 E-mail address: [email protected] (M.E. Romano).
the reproductive years when estrogen levels are highest. There have been isolated case reports of patients with premature thelarche (breast development) and labial adhesions, which would support a multifactorial etiology for labial adhesion formation.3 Inflammation from infection or trauma can erode the epithelium of the labia minora, which, in the absence of estrogen might fuse in the midline. Inflammation might occur as a result of poor perineal hygiene. Stool contamination of the vulva may produce vulvovaginitis and contribute to inflammation. Attention to hygiene may be sufficient for resolution of the adhesions.4 There are certain inflammatory conditions with which labial adhesions have been associated. Lichen sclerosis is associated with labial adhesions as a result of ongoing disease-mediated inflammation. Adhesions typically develop in older patients and are more anterior in location. In a review of the literature, the typical age range for patients with adhesions attributed to lichen sclerosis was between 2 and 10 years of age.1 In patients known to have vulvar dermatoses, careful and regular inspection of the external genitalia is recommended to monitor for the development of labial adhesions. If labial adhesions are found in this subset of patients, referral to a gynecologic provider is recommended. Candidal vulvovaginitis in patients with poorly controlled diabetes mellitus, recent antibiotic use, or in infants with frequent diaper rashes can also be a contributing factor.5 Other infectious etiologies predispose to adhesionsdmost commonly group A Streptococcus after a vulvovaginal skin infection. Although vaginal infection with Neisseria gonorrhea, Gardnerella vaginalis, Chlamydia trachomata, or Trichomona vaginalis in children are less common, they can be etiologies of chronic vulvar inflammation and labial adhesions.5 Any sexually transmitted infection in this population necessitates consideration of sexual abuse.5
1083-3188/$ - see front matter Ó 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jpag.2015.04.010
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Table 1 Pathophysiology of Labial Adhesions Poor perineal hygiene Trauma Straddle injury Female circumcision Sexual abuse Excessive perineal cleaning Infection Candida Group A Streptococcus Neisseria gonorrhea Gardnerella vaginalis Chlamydia trachomata Trichomona vaginalis Vulvar dermatoses Lichen sclerosis Mechanical factors Diaper use
Genital trauma can also lead to labial adhesions. This can be the result of female circumcision or a straddle-like injury. Labial adhesions have been documented in patients with a history of sexual abuse.6 Multiple studies have attempted to document the genital examination findings in patients with suspected sexual abuse. However, it has been difficult to establish a reliable consensus on physical examination findings in this setting.6 Partial labial adhesions was reported in a case control study as a statistically significant physical finding among Caucasian patients with a reported history of abuse.6 Other patient populations demonstrated no difference between abuse patients and control participants. The most common finding in this study was vaginal discharge.6 In evaluation of a patient with labial adhesions it is important for every provider to ask about the possibility of sexual abuse and exclude this as the cause for labial adhesions. Finally, labial adhesions have also been attributed to mechanical factors. Adhesions are uncommon after 6 years of age although for most girls puberty and an increase in estrogen production do not occur for many years.2 Physical apposition of the labia minora in diaper-wearing girls is thought to facilitate the development of adhesions in some cases. Decreased diaper use and increased ambulation allow for more physiologic separation of the labia minora, which reduces the possibility of adhesions (Table 1).7
A
Clinical Presentation and Diagnosis
Labial adhesions are often asymptomatic and diagnosed in a routine genital examination (Fig. 1A). When symptomatic, patients with adhesions may present with abnormal voiding, postvoid urinary dribbling, vaginal pain or discharge, and urinary tract infections. Among patients with labial adhesions, the prevalence of symptoms is not consistently reported. A 2009 retrospective study investigated 151 patients (ages 0.25 to 8.75 years) with labial adhesions. In those patients symptoms were reported as follows: 7.3% with urinary frequency, 19.9% with urinary tract infections (confirmed with positive urine culture), 8.6% with vaginitis, and 12.6% with postvoid dripping. Approximately 50% of patients were asymptomatic.2 The diagnosis is made using close clinical inspection. The degree of adhesions can range from the entire length of the labia minora to only a small portion. There is a midline area of clear, fibrotic tissue (which appears gray) at the site of adhesion, referred to as the raphe. Partial adhesions more commonly occur posteriorly and may completely occlude the vaginal opening. In these patients, absence of the vagina and an imperforate hymen must be excluded. Close inspection and identification of the absence of hymeneal tissues (which is covered by the adhesions) and a midline raphe can help to distinguish labial adhesions from absence of the vagina.8 Rarely, with more extensive adhesions there might be complete blockage of the urogenital opening, including the urethra.8 Although underlying pathology is often not determined in patients with labial adhesions, patients with additional or atypical findings (older age, anterior location, signs of systemic medical disorders and/or dermatological conditions) at presentation require further workup and evaluation. Symptoms suggestive of infection (dysuria, vaginal discharge, or erythema) should prompt an evaluation for underlying infection with urine and/or vaginal cultures. Treatment Observation
Currently, conservative management is considered the most appropriate approach.9,10 In asymptomatic patients with labial adhesions without urinary retention or
B
Fig. 1. (A) Gentle labial traction to evaluate and confirm labial agglutination. This same traction assists separation during the application of topical medications. (B) A cotton-tipped applicator can also be used to assist with gentle separation.
J.L. Bacon et al. / J Pediatr Adolesc Gynecol xxx (2015) 1e5
infection, observation without intervention should be considered. Most patients will have spontaneous resolution of the adhesions when endogenous estrogen production begins. Resolution without therapy has been noted to be as high as 80% within 1 year.11 Refraining from active intervention might be most appropriate in asymptomatic girls who wear diapers, because this group has the highest rate of recurrence. A study by Leung et al (35 girls, 13-23 months of age) showed a recurrence rate of 41% in patients followed 2-72 months after treatment of any kind.12 Estrogens
Traditionally, the treatment for labial adhesions has been use of topical estrogens, with or without manual separation in the office setting.9 When therapy is appropriate, topical estrogen preparations, such as conjugated estrogen vaginal cream (Premarin Vaginal Cream; Pfizer) or estradiol (0.01%) vaginal cream (Estrace Vaginal Cream, USP, 0.01%; Warner Chilcott) remain the first-line medical treatment. Estradiol vaginal cream contains 0.1 mg estradiol in a nonliquifying base composed of water, propylenegylcol, and other compounds, and lacks alcohols that might cause the burning or discomfort of some other preparations. The application of topical estrogen is most appropriate when applied in scant amounts to the midline raphe.8,13 Application might be by fingertip or Q-tip, once or twice a day. Gentle traction, during application of the cream, increases the rate of separation of the adhesions (Fig. 1A). The duration of therapy has varied in studies ranging most commonly from 2 to 6 weeks. A direct relationship between the length of therapy and resolution of adhesions has not been shown. The most common side effects of topical estrogen use include irritation, redness, breast budding, and hyperpigmentation of the vulva. These complications might be minimized with time-limited and appropriate application to avoid unnecessary systemic absorption of estrogen. Rarely, scant vaginal bleeding from stimulation of the endometrium and subsequent shedding have been reported. These side effects are transient and usually resolve after use of the preparation has been discontinued.12,14 Monitoring of breast bud resolution after therapy discontinuation is recommended.8 Resolution of labial adhesions with topical estrogen is reported to be as high as 50%-89%. Success rates also appear to be the highest in female patients with a thin, translucent raphe.10,14,15 Variable results in the literature might reflect the composition and the size of the study groups, suspected duration and thickness of the adhesions, history of recurrence, and previous therapy success. Steroids
Topical betamethasone 0.05% is an alternative for the management of labial adhesions. The basis for the original consideration of this medication was a high rate of success as a nonsurgical method of managing phimosis in young boys.16 Twice daily application combined with gentle traction was successful in 67%-95% of
3
boys.16 An initial small sample of girls with labial adhesions treated with topical 0.05% betamethasone as a therapy for recurrent adhesions or for patients in whom treatment with topical estrogen cream had failed, obtained 68% success in resolution of the adhesions after twice daily application to the raphe for 4-6 weeks.17 Even when topical betamethasone 0.05% was used for up to 3 treatment courses, researchers noted enhanced resolution of the labial adhesions without side effects.18 Another retrospective study suggested that application of 0.05% betamethasone resulted in earlier resolution of labial adhesions with less recurrence compared with topical estrogen therapy.2 Short-term side effects of betamethasone include erythema, pruritus, and folliculitis, skin atrophy, or fine hair growth. Manual Separation
Adhesions of rapid onset, those accompanied by severe symptoms such as urinary retention, adhesions for which medical therapy has failed, or those that appear thick without a visible transparent raphe might be primarily or secondarily treated with manual separation. If the treating provider is uncomfortable or inexperienced with manual separation techniques, a referral to a physician or provider with expertise in pediatric and adolescent gynecology might be considered. Manual separation performed by pulling the labia apart without topical anesthetic or sedation is unnecessarily painful and potentially traumatic for the child and therefore this technique should not be performed. Recurrent forceful separation might result histologically in thicker, more resistant adhesions hypothesized to be associated with bleeding, inflammation, fibrosis, and a potential for increased rates of recurrence.17,18 Surgical separation is best performed using application of a topical anesthetic. Approximately 5-10 minutes after application of lidocaine ointment 2% or 5% or 30 minutes after application of EMLA (a topical prilocaine 2.5%/lidocaine 2.5% combination; APP Pharmaceuticals) the separation can be attempted. The product insert for prilocaine/lidocaine contains recommended dosing for children based on age and weight in kilograms. Medical sedation in an outpatient setting or operating room might be considered for patients unable to tolerate an office procedure.19,20 No specific technique of surgical separation has been studied, nor do most studies provide details of the methods used, but textbooks describe use of a lubricated Q-tip inserted into the opening in the adhesions and pulled along the raphe (see Fig. 1B). Making the initial separation with a sharp blade and gently pulling a Q-tip or probe forward has been mentioned. These gentle techniques attempt to minimize tissue trauma and therefore recurrent adhesions. Magnification with operating loupes or a colposcope might be helpful. When separation has been accomplished, application of topical estrogen has been demonstrated to enhance epithelialization and healing. Topical treatment with estrogen is recommended for several weeks, once or twice daily. The frequency of application and duration of postoperative therapy has not been specifically studied, but 2-4 weeks is most commonly cited.21 After this time, attention to perineal cleaning and application of a bland emollient for
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Table 2 Labial Adhesions: Management Options Asymptomatic Patients Symptomatic patients (mild)
Symptomatic patients (moderate/severe; nonresponse to medical therapy)
Conservative Therapy. Optimize Vulvar Hygiene (A) Topical estrogen, 1 to 2 times daily for 2 to 6 weeks (B) Topical steroids. May use as first-line therapy or as an adjuvant to topical estrogen. May also use if treatment with topical estrogen fails. One to 2 times daily for 4 to 6 weeks Referral to a specialist for manual separation Manual separation should be performed with topical anesthetic with or without adjunctive sedation To limit recurrence of adhesions, topical estrogen should be used followed by extended use of bland emollients
several months has also been recommended, although the exact duration to best decrease recurrence of labial adhesions has not been defined (Table 2).8,9,14
separation using topical anesthesia with or without adjunctive sedation. Level C
Recurrence III
The reported incidence of recurrent labial adhesions varies widelyd7%-55% in a case series. Because of the high rates of recurrence, parents should be informed about the possibility of recurrence during the course of treatment. Risks for recurrent adhesions decrease with increasing age, and are lowest after production of endogenous estrogen begins.2,11,17,18,22,23 Patients prone to recurrent labial adhesions might have had thick adhesions with a less visible midline raphe. Factors that contribute to recurrent adhesions include poor perineal hygiene, vigorous cleansing techniques, trauma, recurrent genital infections, or persistent medical or dermatological disorders.9 The initial method of treatment has not been shown to be a contributing factor to recurrent disease.8,10 The management of recurrent adhesions should include the same treatment considerations used for treatment of the initial adhesions: conservative therapy (optimize vulvar hygiene) with observation and topical estrogen or betamethasone 0.05% with repeat manual separation if needed.8,10,17 Management of recurrent adhesions has been less well studied than treatment of initial adhesions. One retrospective study showed that re-treatment of persistent or recurrent labial adhesions with topical estrogen therapy after detailed application instruction was successful in at least 35% of cases.24 Additional measures to improve perineal care and cleansing and management of any predisposing medical conditions should be emphasized. Recommendations Level A II-2, II-3
Conservative medical therapy without any intervention is recommended in asymptomatic patients. In these patients emphasis should be placed on optimizing vulvar hygiene. In symptomatic patients, short-term treatment with topical estrogen is the best initial therapeutic recommendation. Betamethasone 0.05% is an alternative or adjunctive medical therapy. II-2
Acute onset of adhesions, severe symptoms of urinary retention, recurrent infections, or adhesions not responsive to medical therapy, might be managed with manual
Prevention of recurrent adhesions includes proper genital hygiene, treatment of contributing factors, and postsurgical therapy initially with topical estrogen followed by bland emollients for an extended period of time. Acknowledgment
Education Committee, North American Society of Pediatric and Adolescent Gynecology: Jennifer Dietrich, MD, MSc (co-chair); Judith Simms-Cendan, MD (co-chair); Elise Berlan, MD; Jennifer Bercaw-Pratt MD; Lisa Jacobsen, MD, MPH; Saifudden Mama, MD, MPH; Maria Rahmandar, MD; Amy Sass, MD; Hina Talib, MD; and Andrea Zuckerman, MD. References 1. Gibbon K, Bewley A, Salisbury J: Labial fusion in children: a presenting feature of genital Lichen Sclerosis? Pediatr Dermatol 1999; 16:388 2. Mayoglou L, Dulabon L, Martin-Alguacil N, et al: Success of treatment modalities for labial fusion: a retrospective evaluation of topical and surgical treatments. J Pediatr Adolesc Gynecol 2009; 22:247 3. Papagianni M, Stanhope R: Labial adhesions in a girl with isolated thelarche: the importance of estrogenization. J Pediatr Adolesc Gynecol 2003; 16:31 4. Eroglu E, Yip M, Oklar T, et al: How should we treat prepubertal labial adhesions? Retrospective comparison of topical treatments: estrogen only, betamethasone only, and combination estrogen and betamethasone. J Pediatr Adolesc Gynecol 2011; 24:389 5. Randelovic G, Mladenovic V, Risti c L, et al: Microbiological aspects of vulvovaginitis in prepubertal girls. Eur J Pediatr 2012; 171:1203 6. Berenson A, Chacko M, Wiemann C, et al: A case- control study of anatomic changes resulting from sexual abuse. Am J Obstet Gynecol 2000; 182:820 € rk O, et al: Do hygienic factors affect labial fusion 7. Acer T, Otgun I, Oztu recurrence? A search for possible related etiologic factors. J Pediatr Surg 1913; 2012:47 8. Quint E: Labial agglutination in a teenager. J Pediatr Adolesc Gynecol 2003; 16:61 9. American College of Obstetricians and Gynecologists (ACOG): Diagnosis and management of vulvar skin disorders. Washington (DC), American College of Obstetricians and Gynecologists, 2008. 11 (ACOG practice bulletin; no. 93. 10. Schroeder B: Pro-conservative management for asymptomatic labial adhesions in the prepubertal child. J Pediatr Adolesc Gynecol 2000; 13:183 11. Pokorny S: Prepubertal vulvovaginopathies. Obstet Gynecol Clin North Am 1992; 19:39 12. Leung A, Robson W, Tay-Uycbo J: The incidence of labial fusion in children. J Paediatr Child Health 2008; 29:235 13. Van Eyk N, Allen L, Giesbrecht E, et al: Pediatric vulvovaginal disorders: a diagnostic approach and review of the literature. J Obstet Gynaecol Can 2009; 31:850 14. Starr N: Labial adhesions in childhood. J Pediatr Health Care 1996; 10:26 15. Aribarg A: Topical estrogen therapy for labial adhesions in children. Br J Obstet Gynaecol 1957; 82:424 16. Kikiros C, Beasley S, Woodward A: The response of phimosis to local steroid application. Pediatr Surg Int 1993; 8:329 17. Muram D: Treatment of prepubertal girls with labial adhesions. J Pediatr Adolesc Gynecol 1999; 12:67 18. Bacon J: Prepubertal labial adhesions: evaluation of a referral population. Am J Obstet Gynecol 2002; 187:327
J.L. Bacon et al. / J Pediatr Adolesc Gynecol xxx (2015) 1e5 19. Acker A, Jamieson MA: Use of intranasal midazolam for manual separation of labial adhesions in the office. J Pediatr Adolesc Gynecol 2013; 26:195 20. Nurzia M, Eickhorst K, Ankem M, et al: The surgical treatment of labial adhesions in pre-pubertal girls. J Pediatr Adolesc Gynecol 2003; 16:21 21. Soyer T: Topical estrogen therapy in labial adhesions in children: therapeutic or prophylactic? J Pediatr Adolesc Gynecol 2007; 20:241
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22. Nowlin P, Adams J, Nalle B: Vulvar fusion. J Urol 1949; 62:75 23. Smith C, Smith D: Office pediatric urologic procedures from a parental perspective. Urology 2000; 55:272 24. Kumetz LM, Quint EH, Fisseha S, et al: Estrogen treatment success in recurrent and persistent labial agglutination. J Pediatr Adolesc Gynecol 2006; 19:381
