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Division of Pediatric Adolescent Gynecology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, Florida
This Clinical Opinion replaces the NASPAG Clinical Recommendation: Pediatric Lichen Sclerosus published in 2014. The objective of this document is to provide guidance in the diagnosis and management of vulvar lichen sclerosus (LS) in the pediatric and adolescent patient in order to treat patient symptoms and reduce long-term sequelae. LS is a chronic inflammatory condition affecting the anogenital region that may present in the prepubertal or adolescent patient. Clinical presentations include significant pruritus, loss of pigmentation and vulvar adhesions with loss of normal vulvar architecture. Management includes topical agents for induction and maintenance therapy, as well as long-term follow-up for identification and treatment of recurrence and sequelae. This document is intended for use by both primary and specialty pediatric and adolescent gynecology (PAG) providers, including specialists in pediatrics, gynecology, adolescent medicine, and dermatology.
Patients with LS should be monitored for symptoms and signs of other autoimmune disorders. (Level II-B)
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Patients with Turner syndrome should be evaluated for LS. (Level II-B)
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Patients diagnosed with LS should be examined for extragenital LS . (Level III)
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LS can be diagnosed in the pediatric/adolescent population without biopsy in patients presenting with the typical symptoms and appearance of LS lesions. Biopsy is indicated for patients with atypical lesions or those not responding to therapy as anticipated. (Level III)
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Initial therapy for LS should be with high-potency topical steroids (Level II-B)
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Limited evidence suggests a role for immune modulators in non-responders and those patients unable to tolerate steroid therapy. (Level II -3 B)
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After induction, maintenence therapy is recommended for 2 years. Patients should be followed at 6–12-month intervals to monitor for symptoms, architectural change, and possible risk of malignancy. (Level III)
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It is imperative caregivers counsel their patients to continue long-term gynecologic observation in order to prevent long term sequelae from occurring, given that symptoms may remit with therapy and vulvar changes may continue to occur. (Level II)
Background
Vulvar LS is a chronic inflammatory skin condition that often presents in prepubertal girls. The purpose of this document is to provide guidance in the diagnosis and management of vulvar LS in the pediatric and adolescent patient in order to treat patient symptoms and reduce long-term sequelae of scarring.
Evidence
A search of PubMed, Cochrane Wiley, and the Cochrane systematic reviews was conducted in January 2021 for English language materials involving human subjects published since 2000 using the following terms: pediatric lichen sclerosus, adolescent lichen sclerosus, childhood lichen sclerosus. Following the search, articles which only addressed male patients were excluded.
Epidemiology
Lichen sclerosus (LS) has been reported in all age groups and both sexes but has a bimodal age distribution in premenarchal and postmenopausal women. A population study in Finland found that although most cases of LS occurred in postmenopausal patients, there was an elevated incidence in childhood of girls aged 5-9 compared to other women under the age of 24 years. 1A study of 44 Finish girls diagnosed under the age of 19 from 1982-2010 found a mean age of onset of symptoms of 7 years, and 86% were prepubertal at the time of presentation.
One often cited estimate of LS prevalence of 1:900 in premenarchal girls was derived from calculating the number of patients found to have LS in a pediatric vulvar clinic divided by the total number of premenarchal girls in the referral area, but true prevalence studies of multiethnic large populations are lacking.
The exact pathogenesis of LS remains unclear and is complex, but it is generally accepted that LS is an autoimmune disorder. In premenarchal girls, LS has been associated clinically and immunologically with autoimmune disorders including thyroiditis, pernicious anemia, psoriasis, vitiligo, morphea, and alopecia areata.
. The genetic contribution to the development of LS remains unclear. Twenty-five percent of girls with LS have a first-degree relative with an autoimmune disorder, and HLA Class II antigen DQ 7 has been found to be prevalent in patients with childhood LS.
Girls and women with Turner Syndrome, who are at risk of autoimmune thyroiditis and other autoimmune disorders, seem to be at high risk of LS as well, with a prevalence of LS in 17% of patients aged 13-52 years.
Other areas under investigation in the pathogenesis of LS include immunocytologic alterations, sex hormone factors, trauma, and connective tissue alterations.
In addition to autoimmune pathogenesis, LS is occasionally believed to be a result of a Koebner phenomenon, which is the occurrence of a lesion as result of skin injury.
Children presenting with LS may have a wide variety of complaints. Typical complaints include vulvar irritation and pain, vulvar pruritus, bleeding due to skin fissures, painful defecation, and constipation.
Most patients have received treatment for vulvovaginal candidiasis, urinary tract infection, or constipation, and some have had vaginal endoscopy prior to the time of diagnosis. The extent of the anogenital lesions does not correlate with the intensity of symptoms; thus, small lesions may result in significant complaints.
Compulsive scratching of genitalia and grabbing at clothing due to itching may be disturbing to parents and teachers and confused with masturbation. The vulvar irritation and pain may be more significant at night.
Older adolescents may present with dyspareunia and lacerations at the base of the posterior fourchette from trauma during intercourse. The anogenital lesions may also be detected incidentally by a parent or physician when the patient is asymptomatic.
The average delay from onset of symptoms to diagnosis is 1 to 2 years .2
In most cases, the diagnosis of LS is made based on history and physical exam findings. The characteristic clinical appearance of LS is ivory white or rose-colored patches. In early LS or in patients with very light skin color, the appearance may be subtle. The border of the hypopigmented area is often indistinct, and the affected lesion can spread to the perineal and perianal regions causing a classic “figure of eight” shape. The patches can be atrophic with a shiny or crinkled “cigarette paper” appearance or can be thickened due to hyperkeratosis as a result of repeated excoriations. The repeated excoriations can lead to ecchymoses, hemorrhage, and superficial erosions (Figures 1 and 2). Telangiectasias and fissures can also occur. The superficial erosions can be painful and put patients at risk for secondary superimposed infection. Infantile perianal protrusions, also called infantile pyramidal protrusions, are not diagnostic of but can be found in conjunction with LS due to the association with constipation.
Secondary to skin changes described above, genital scarring may develop, which can result in labial and clitoral hood adhesions, a buried clitoris, loss or attenuation of labia minora, and narrowing of the vaginal introitus (Figure 3).
Extragenital LS (Figure 4) has been found in 18% of pediatric LS patients, most commonly on the trunk and extremities. Oral LS has also been described in both pediatric and adult patients, and appears as irregular whitish patches on the lips and buccal mucosa.
Table 1 describes other childhood vulvar disorders often considered in the differential diagnosis of LS. Vitiligo is most often confused with LS due to the hypo- or depigmentation; however, patients with vitiligo demonstrate skin depigmentation that is sharply demarcated, occurs in a patchy distribution, and is typically asymptomatic without evidence of vulvar atrophy or structural changes. A case series described persistent depigmentation in patients with LS who have been treated and are asymptomatic, suggesting that there may be an overlap in diagnoses, known as vitiligoid LS, especially in girls with darker skin (Figure 5).
Lichen planus, a similar immune-mediated inflammatory disorder affecting the vulva, is rare in children and more typically presents in the peri- and post-menopausal years. LS is not associated with vaginal mucosal involvement and rarely affects the oral mucosa, whereas lichen planus typically involves the oral and vaginal mucosa.
Sexual abuse and LS are not mutually exclusive, so both diagnoses should be considered. If there is any concern for sexual abuse, the child should be evaluated jointly with a healthcare provider who is appropriately trained in child abuse evaluation and management. (Chart 1)
Table 1Differential Diagnosis of Pruritic Vulvar Dermatoses in the Pediatric Population
Differential Diagnosis of Pruritic Vulvar Dermatoses in the Pediatric Population
Disorder
Distinguishing Features
Lichen sclerosus
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Figure of 8 lesion with loss of pigmentation
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Fissures and pyramidal protrusions
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Excoriation and purpura can be present from scratching
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Extragenital lesions in 18%
Atopic dermatitis/Eczema
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Irregular border, erythema and scaling of lesion
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Can have endogenous/exogenous triggers
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Commonly have history of extra-vulvar dermatitis
Irritant contact dermatitis
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Erythematous lesions usually in distribution of contact with pads or diapers, may develop ulcerations or pseudo-verrucous changes if chronic
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May be caused by urinary incontinence chronic moisture exposure
Vitiligo
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Asymptomatic loss of vulvar pigmentation
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Often asymmetric, sharply demarcated and patchy distribution
Psoriasis
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Intense erythema with discrete borders and silvery scale
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Usually extra-vulvar manifestations on knees and elbows
Candidiasis
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Very uncommon in hypoestrogenic, immunocompetent patients
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Erythema with satellite lesions present
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May be seen with diaper use and superimposed on irritant contact dermatitis
Trauma/abuse
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Scarring from previous trauma or ecchymoses from acute injury
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History of abuse or trauma should match appearance
In most children, the lesion can be diagnosed based on clinical exam and the patient treated with a trial of therapy first. Biopsies are rarely necessary in these patients. If the treatment fails or the diagnosis is in doubt, referral to or image consultation with a pediatric dermatologist or pediatric gynecologist knowledgeable in vulvar disorders should be considered. The threshold for vulvar biopsy in children is much higher than in post-menopausal women due to the increased challenges (e.g. need for sedation, discomfort) of performing biopsies in children and the decreased risk of malignancy in this younger age group. However, in patients who are refractory to therapy a biopsy may be indicated. Consideration for the variable biopsy techniques in pediatric patients may require collaboration with a dermatologist or pediatric gynecologist. The findings in the pediatric population are similar to the characteristic histologic findings in adults, including thinning of the epidermis, loss of rete pegs, hydropic degeneration of basal cells, hyperkeratosis, a wide band of collagen beneath the dermo-epidermal junction, and lymphocytic infiltrate.
The goals of therapy are relief of symptoms, resolution of atrophic changes, prevention of scarring and anatomic distortion. Unfortunately, randomized controlled trials for LS therapy in children and adolescents do not exist. The mainstays of therapy include management of symptoms, topical high potency corticosteroids and alternatively topical immune modulators for both induction and maintenance therapy. Based on available evidence, suggested algorithm for management can be seen in Figure 6. Topical testosterone, dihydrotestosterone and progesterone should not be used in adults or children as a Cochrane found that topical androgens are ineffective for treatment of LS in adults, and their use has not been studied in pediatric patients.
The ultra-potency topical corticosteroids (UPTC) clobetasol propionate and augmented betamethasone dipropionate are the most commonly used medications for treatment of LS. Prolonged use of topical steroids can be associated with thinning of the dermis, secondary superimposed infections, and rarely hypothalamic-pituitary-adrenal (HPA) axis suppression.27Although there has been concern about use of UPTC in the pre-pubertal population due to the relatively atrophic hypoestrogenic skin and theoretical risk of increased absorption, studies have found use of topical steroids safe in this population as modified mucous membranes of the vulva (non-hair-bearing) are relatively resistant to atrophic changes from steroid use.
A meta-analysis of HPA axis suppression in children using topical corticosteroids provided reassuring evidence that long-term use of low to mid potency topical steroids in children has a very rare risk of reversible clinical adrenal insufficiency, and very small risk in children using ultra potent topical steroids, and did not recommend routine HPA testing for children receiving therapy.
Ointments are generally recommended because of their increased penetrance and decreased risk of contact dermatitis as they tend to be less irritating on inflamed and genital skin than creams, which tend to be alcohol-based. Rarely, if a contact dermatitis develops due to sensitivity to the vehicle in which the steroid is suspended, the physician may consider a referral to a compounding pharmacy to create the steroid with a hypoallergenic vehicle. Corticosteroid treatment regimens reviewed ranged from weekly administration to twice-daily application with UPTC tapering varying from decreased frequency to decreased potency or both. In general, one month after initiating treatment, the patient should be seen to evaluate the compliance with and response to treatment along with possible side effects.
See Table 2 for selected studies of corticosteroid treatment for LS. In 2011 a Cochrane Review by Chi, Kirtschig et al. addressed the most common treatments and their efficacy in adults but did not have enough patient numbers to make specific recommendations for children.
Prospective case series and retrospective chart review
UPTC versus MPTC for induction therapy and maintenance
Higher response rate in UPTC in induction (96% marked improvement, 72% complete), less frequent use of UPTC v MPTC needed for maintenence, lower total steroid dose with UPTC
Tacrolimus induction x 16 weeks; then maintenance 6 months for subset
Treatment effect was greatest at 16 weeks v. 8 weeks, prevention of recurrences much greater in girls who received long term maintenance therapy (80% v 22%).
Induction with ultra or moderate potency, maintenance with mid or mild potency corticosteroid
94% adhering to maintenance had disease control, 69% of patients nonadherent with maintenance had signs of disease, some with scarring. Long term topical steroid well-tolerated
A retrospective analysis of pediatric patients with lichen sclerosus treated with a standard protocol of class I topical corticosteroid and topical calcineurin inhibitor.
Journal of dermatological treatment.2016; 27(Level II-3): 64-66
Topical calcineurin inhibitors, pimecrolimus and tacrolimus, have also been used for treatment of LS. Theoretical advantages are decreased systemic immunosuppression and decreased risk for atrophic changes in the local skin. Data regarding use of immune modulators is limited, but there have been multiple case reports of success with use of topical calcineurin inhibitors. See Table 2. Studies comparing pimecromlimus to clobetasol in adult women with lichen sclerosus show equivalent efficacy.
Both pimecrolimus and tacrolimus have an FDA black box warning concerning a possible causal relationship between long term use of oral calcineurin inhibitors and skin cancer and lymphoma. There has been no evidence that the topical calcineurin inhibitors increase the risk of cancer. Due to the black box warning and the known effectiveness of very high potency steroids, it may be best to consider both pimecrolimus and tacrolimus as second line agents. Additionally, initial application of calcineurin inhibitors may cause a burning sensation and cooling medication in a refrigerator prior to use may mitigate this possibility. Neither pimecrolimus nor tacrolimus are recommended to be used in children under the age of 2.
Symptom management
Many patients continue to have some mild itching and discomfort despite appropriate treatment. Often supportive measures such as good vulvar hygiene, and cool compresses can offer temporary, episodic relief. A cool compress can be made with chilled water on a clean washcloth and patients can hold it on their vulva as needed; ice or frozen compresses should not be used on the vulva. Vulvar irritation may be treated with a hypoallergenic topical petroleum-based emollient such as Vaseline or a zinc-based barrier cream. Peri bottle use can assist with irritation with voiding, and cool compresses can relieve irritation. Topical anesthetics can also be used but may be associated with contact dermatitis. Insomnia caused by vulvar pruritus may be treated with antihistamines such as diphenhydramine and hydroxyzine.
Persistent vulvodynia may be treated with antidepressants such as tricyclic antidepressants or serotonin reuptake inhibitors and antiepileptic drugs such as gabapentin.
Given evidence that LS does not always remit in puberty and has a high frequency of relapse, it is prudent to consider options for maintenance therapy to decrease long-term sequelae.
A retrospective analysis of pediatric patients with lichen sclerosus treated with a standard protocol of class I topical corticosteroid and topical calcineurin inhibitor.
Journal of dermatological treatment.2016; 27(Level II-3): 64-66
Studies have shown successful induction with UPTC followed by corticosteroid taper for maintenance, as well as induction with tacrolimus and taper to decreased frequency of use for maintenance. See Table 2. Both regimens reduced disease recurrence and limited progression of scarring. Anderson studied a combination regimen utilizing high potency corticosteroids for induction therapy followed by topical calcineurin inhibitors for maintenance. This combination demonstrated efficacy at resolving initial symptoms while limiting side effects of long-term steroid use. Tacrolimus also reduced the risk of scarring and anatomic changes associated with LS.
A retrospective analysis of pediatric patients with lichen sclerosus treated with a standard protocol of class I topical corticosteroid and topical calcineurin inhibitor.
Journal of dermatological treatment.2016; 27(Level II-3): 64-66
In summary, a combined therapy utilizing UPTC daily for 4 weeks or until disease/symptom control followed by daily topical calcineurin inhibitor or topical steroid taper for maintenance. If re-evaluation after 6 months of maintenance therapy demonstrates no progression of disease, yearly observation for an additional 2 years is recommended. If symptoms and disease are well controlled, consider discontinuing therapy.
Though there is no consensus on a superior maintenance regimen, several studies have shown significant suppression of disease with maintenance regimens in general.
A retrospective analysis of pediatric patients with lichen sclerosus treated with a standard protocol of class I topical corticosteroid and topical calcineurin inhibitor.
Journal of dermatological treatment.2016; 27(Level II-3): 64-66
See Table 4 for suggested induction and maintenance regimens based on the current available evidence.
Table 4Induction/Maintenance in order of preferred options.
Induction options
Maintenance options
UPTC daily therapy for up to 4 weeks
Low to moderate potency topical corticosteroid daily to twice weekly
UPTC daily for 4 weeks or until disease/symptom control
Daily topical calcineurin inhibitor, weaning to twice weekly.
Calcineurin inhibitor twice daily for up to 16 weeks
Calcineurin inhibitor twice weekly
Re-evaluation should occur at 6 months after switching to maintenance therapy. Maintenance therapy should be continued for 2 years, and if in remission, at least annually.
Surgery for LS is usually reserved for complications due to adhesions and scarring. Atrophy of the labia minora, scarring of the clitoral hood and labial/clitoral hood adhesions have been described.
These complications can lead to urinary tract outflow obstruction, retention pseudocysts, and dyspareunia. Surgical procedures are typically performed to release adhesions and scarring through the use of sharp dissection or laser
One case series of surgical treatment of adolescents with significant pain due to labial and clitoral adhesions included placement of Surgicel® (an oxidized cellulose polymer) at the surgical site with no recurrence of adhesions at 1 year.
Although two case series in postmenopausal patients show relief of LS symptoms refractory to corticosteroid treatment, there are no studies using fractional microablative CO2 laser therapy for LS in the pediatric population, precluding evidence-based recommendations.
Effect of rescue fractional microablative CO2 laser on symptoms and sexual dysfunction in women affected by vulvar lichen sclerosus resistant to long term use of topical corticosteroid: a prospective and longitudinal study.
It was previously thought that the condition resolved with puberty, but studies have shown that the symptoms and signs of the disease persist after puberty in a majority (75%) of patients.
Focseneanu et al. published a long-term follow-up study of 36 girls diagnosed with pre-pubertal LS. They conducted phone interviews to evaluate patients’ perceptions of symptoms and need for further treatment with a mean duration of 5 years after diagnosis.
Remission was achieved in 83%, most often following treatment with high potency topical steroids, but relapse occurred in 44%. Intermittent maintenance was required for 3.1 years on average with a mean average length of remission of 3.6 years.
Long-term sequelae
Given that symptoms may remit with therapy in the pediatric population, it is imperative caregivers counsel their adolescents to continue long term gynecologic observation in order to prevent long term sequelae from occurring. Often, symptoms of pruritus and pain can be effectively treated and resolve with high potency corticosteroid use; however, long-term architectural changes often persist. Continued observation or maintenance therapy is prudent to avoid further anatomical distortion. Clitoral phimosis, labial resorption and labial adhesions are the most commonly noted long term sequelae of suboptimal treatment of LS.
Genital lichen sclerosus in childhood and adolescence- a retrospective case series of 15 patients:early diagnosis is crucial to avoid long-term sequelae.
Other long-term consequences can include effects on sexual function, self-image, and potential for impaired perineal scar healing after obstetric laceration.
Long term follow-up of pediatric patients into adulthood has only been published in case reports; however, these long -term consequences have been studied in adult populations. Women with LS have a lower frequency and quality of sexual activity and less frequent orgasm when compared to healthy controls.
Squamous cell carcinoma is believed to develop via two independent pathogenic pathways. The most commonly recognized pathway is associated with the HPV virus and termed HPV-associated usual vulvar intraepithelial neoplasia (VIN). The HPV independent pathway, also known as HPV-independent differentiated VIN, has been proposed to have LS as a precursor.
It is unknown at this time if children and adolescents diagnosed with LS are at increased risk. Although the biology of increased malignancy risk in the setting of chronic inflammation would suggest that well-controlled LS would have a lower risk of malignancy, there are no long-term studies validating such an assumption. Until more long-term studies are complete, and the risk is better quantified, it may be best to advise parents of the possible risk for vulvar cancer associated with LS and to stress the importance of long-term follow up to the patients’ parents with visits recommended every 6-12 months.
There is a paucity of data for duration of LS follow-up in patients diagnosed with LS in childhood. Although HPV is not believed to be a part of the pathogenesis of LS associated squamous cell carcinoma of the vulva, all adolescent patients should be encouraged to complete the HPV vaccination series for the prevention of both cervical cancer and HPV related squamous cell carcinoma of the vulva.
Conclusion
LS is a chronic condition commonly affecting pre-pubertal females that can be asymptomatic or associated with vulvar complaints. It can result in decreased quality of life along with vulvar atrophy and scarring. Treatment is usually a course of a high potency corticosteroid for induction followed by maintenance therapy to reduce sequelae. Long-term follow up is recommended.
Summary of Recommendations
Studies were reviewed and evaluated for quality according to the method outlined by the U.S. Preventive Services Task Force:
I Evidence obtained from at least one properly designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled trials without randomization.
II-2 Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.
II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.
III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Acknowledgements
This document was developed with the support of the Education Committee Subcommittee on Clinical Opinions, which in addition to the authors Dr. Simms-Cendan and Dr. Hoover, also include Sloane Berger-Chen MD, Stephanie Cizek MD, Frances Grimstad MD, Fareeda Haamid MD, Amy Sass MD MPH, Nicole Todd MD.
Disclosure
The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.
References
Halonen P
Jakobsson M
Haikinheimo O
et al.
Incidence of lichen sclerosus and subsequent causes of death: a nationwide Finnish register study.
A retrospective analysis of pediatric patients with lichen sclerosus treated with a standard protocol of class I topical corticosteroid and topical calcineurin inhibitor.
Journal of dermatological treatment.2016; 27(Level II-3): 64-66
Effect of rescue fractional microablative CO2 laser on symptoms and sexual dysfunction in women affected by vulvar lichen sclerosus resistant to long term use of topical corticosteroid: a prospective and longitudinal study.
Genital lichen sclerosus in childhood and adolescence- a retrospective case series of 15 patients:early diagnosis is crucial to avoid long-term sequelae.
Disclaimer: This Clinical Opinion has been prepared by Judith Simms-Cendan, MD, and Kim Hoover, MD with expert review by Kalyani Marathe, MD and Kelly Tyler, MD. This document has been reviewed and approved by the North American Society of Pediatric and Adolescent Gynecology (NASPAG) Education Committee, approved by the JPAG Editor in Chief, and by the NASPAG Board of Directors. This Clinical Opinion reflects currently available best evidence for practice at the time of publication and is designed to aid practitioners in making decisions about appropriate patient care but should not be construed as dictating an exclusive course of management. Variations in practice may be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice.
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