Presenting symptoms and diagnosis of vulvar lichen sclerosus in
premenopausal women: a cross-sectional study
Jill M. Krapf MD MEd, Alyssa B. Smith MD, Sarah T. Cigna MD, Andrew T.
Goldstein MD
Jill M. Krapf MD MEd
Center for Vulvovaginal Disorders, Washington DC
The George Washington University School of Medicine and Health Sciences,
Department of Obstetrics and Gynecology, Washington DC
Alyssa B. Smith MD
The George Washington University School of Medicine and Health Sciences,
Department of Obstetrics and Gynecology, Washington DC
Sarah T. Cigna MD
The George Washington University School of Medicine and Health Sciences,
Department of Obstetrics and Gynecology, Washington DC
Andrew T. Goldstein MD
Center for Vulvovaginal Disorders, Washington DC
The George Washington University School of Medicine and Health Sciences,
Department of Obstetrics and Gynecology, Washington DC
Corresponding Author:
Jill M. Krapf MD MEd
Associate Director Center for Vulvovaginal Disorders, Washington DC
3 Washington Circle NW, Suite 205
Washington DC 20037
Telephone:
E-mail:
jillkrapfmd@gmail.com
Running Title: vulvar lichen sclerosus in premenopausal women
Abstract
Objective: Characterize the presentation of vulvar lichen scleorsus (LS)
among premenopausal women.
Design: Cross-sectional study.
Setting: An international web-based survey distributed on social media
support groups and in two urban gynecology offices specializing in LS.
Population: A total of 503 premenopausal women with biopsy-confirmed
vulvar LS between the ages of 18-50.
Methods: Participants completed an anonymous 28-question web-based
survey between January to March 2021.
Main Outcome Measures: Symptoms, timing and accuracy of diagnosis, and
presence of concomitant autoimmune conditions.
Results: Symptoms reported to be most present and affect the individual
were dyspareunia (68%; 44%) and tearing with intercourse or vaginal
insertion (63%; 39%). Symptoms that most frequently prompted patients
to seek medical attention were dyspareunia (35%), pruritus (31%), and
tearing with intercourse or vaginal insertion (26%). Most common skin
changes included hypopigmentation (81%), vulvar fissures (72%) and
labial resorption (60%), with fissures affecting the individual the
most (48%). There was a 4-year delay in diagnosis with an average age
of symptom onset of 27 years and average age of diagnosis of 32 years.
Sixty-six percent of respondents initially received an alternative
diagnosis, most commonly vulvovaginal yeast infection (49%). There is
an increased incidence of hypothyroidism, vitiligo, pernicious anemia,
and celiac disease.
Conclusion: Premenopausal women with vulvar LS more commonly present
with dyspareunia and tearing with intercourse, less often than vulvar
pruritis. This condition should be considered and evaluated in women of
all ages presenting with vulvar symptoms and sexual pain.
Funding: None
Keywords: lichen sclerosus; vulvar dermatoses; vulvar pruritis;
dyspareunia
Tweetable Abstract (107 characters): Premenopausal women with vulvar
lichen sclerosus, an overlooked demographic, most often present with
dyspareunia, not itch
Presenting symptoms and diagnosis of vulvar lichen sclerosus in
premenopausal women: a cross-sectional study
INTRODUCTION
Lichen sclerosus (LS) is a chronic, inflammatory skin condition that
primarily affects the anogenital epithelium in women. It has been long
thought that LS presents in a bimodal distribution in premenarchal girls
and postmenopausal women, largely sparing reproductive aged women.
However, it has recently been reported that up to 40% of women will
display cutaneous changes and onset of symptoms due to LS during their
reproductive years.1 Although LS is generally
considered to be uncommon, one study conducted by practitioners
experienced in vulvar dermatoses, found an incidence of one in 70 in
women presenting to a general gynecologic practice, and 46% of those
affected were premenopausal.2
Premenarchal girls may present with symptoms including pruritus,
dysuria, constipation, vulvar pain, and bleeding.3,4Similarly, the most common presenting symptom in postmenopausal women is
severe pruritis, often accompanied by dyspareunia and
bleeding.5-7 Reviews have found that less than 10% of
children and adolescents are asymptomatic in
presentation.3,6 In a cohort of women with LS that
included 46% premenopausal women, 39% of women were asymptomatic in
the setting of advanced disease.2
Clinically, specialists in LS have observed that women of reproductive
age often present with tearing and skin changes, rather than itch, as
their primary symptoms. Vulvar pruritis is often described in conditions
associated with low estrogen, such as genitourinary syndrome of
menopause. A study of reproductive age women with “early onset” LS
indicated that the use of androgenic oral contraceptive pills was
associated with symptoms and diagnosis of vulvar LS.8It is possible that decreased clarity in the presenting symptoms of
vulvar LS, specifically in estrogenized women, may contribute to the
known five-year delay in diagnosis of this
condition.9,10
There is a paucity of literature on presenting symptoms of vulvar LS
specific to premenopausal women. Women of reproductive age may have
different presenting symptoms than premenarchal girls or postmenopausal
women. The purpose of this web-based observational study is to
characterize the presentation of vulvar LS among premenopausal women.
METHODS
This cross-sectional study of LS among reproductive age women was
approved by the George Washington University Institutional Review Board
(#NCR202909). The study involved a 28-question online survey that was
developed by two board-certified Obstetrician Gynecologists specializing
in vulvar dermatoses. The questionnaire included Yes/No, multiple
answer, and free-text responses. Demographic data included age,
ethnicity, and level of education. Questions characterized symptoms
experienced, which symptoms prompted medical attention, and which
symptoms affected the participant the most. Information regarding time
between symptom onset and diagnosis, alternative diagnoses, and
additional autoimmune conditions was collected. The questionnaire was
written in English.
The link to the secure survey was distributed on social media though
four closed private Facebook support groups for LS. These groups have
1800, 4500, 3900, and 13,000 international members, respectively. It was
also shared on women’s sexual health pages on Instagram, as well as the
Reddit subthread r/lichensclerosus with over 1300 members. In addition,
the survey was shared with patients at two gynecology offices that
specialize in vulvar conditions in Washington, D.C.. Survey data were
collected over a period of seven weeks from January
9th 2021 through March 1st 2021 and
managed using the secure web application Research Electronic Data
Capture (RED-Cap) hosted at Children’s National Medical Center
(Washington, D.C.).
Inclusion criteria were a diagnosis of vulvar LS confirmed with vulvar
biopsy and age of 18-50 at the time of the study. Participants over the
age of 50, those reporting menopausal status, or those stating not to
have had a vulvar biopsy or a vulvar biopsy inconsistent with LS were
excluded from data analysis.
Numerical data were expressed as mean +/- standard deviation. Bivariate
Pearson correlation was used to determine the relationship between age
of symptom onset and time interval to diagnosis. The prevalence of other
autoimmune diseases within the general population were collected as
reported by recent review articles in the
literature.11-17 When comparing prevalence of
autoimmune diseases to the prevalence reported in our survey population,
a Chi-Square test was used to analyze statistical significance. The
values P < 0.05 were considered statistically significant.
RESULTS
A total of 956 responses to the survey were received. Of these
responses, 910 met inclusion criteria for age and premenopausal status
and 46 were excluded for age >50 years. A total of 503
respondents who met initial inclusion criteria reported a
biopsy-confirmed diagnosis of LS (Figure 1).
The demographics are shown in Table 1, with 87% white, 4% Latina or
Hispanic, 2% Asian, and 1% black. The mean age of the population was
37 years, with a range from 19-50 years (Table 1). Of those who provided
specific information about symptom onset and diagnosis, the average age
of symptom onset was 27 years (range 0-47 years) and average age of
diagnosis was 32 years (range 2-50 years) . The population
reported a mean duration of symptom onset to diagnosis of four years
(range 0-37 years). Notably, 43% of individuals reported experiencing
symptoms as a child (Table 2). There is an inverse correlation between
the age at which symptoms began and the time interval to diagnosis with
a Pearson correlation coefficient of -0.487 (t (455)=14.184,p <.0001; Figure 2).
The most prevalent symptoms among this population were dyspareunia
(68%), tearing with intercourse or insertion (63%), and decreased
clitoral sensation (35%). Dyspareunia (44%) and tearing with
intercourse or vaginal insertion (39%) were noted to affect respondents
the most. Symptoms that most frequently prompted patients to seek
medical attention were dyspareunia (35%), pruritus (31%), and tearing
with intercourse or vaginal insertion (26%) (Table 3; Figure 3).
In regard to vulvar skin changes, respondents endorsed hypopigmentation
(81%) and the architectural changes of labial resorption (60%) and
vulvar fissures (72%) most commonly. Although fissures (39%) and
hypopigmentation (31%) most frequently prompted individuals to seek
medical evaluation, fissures reportedly affected individuals the most
(48%) (Table 4; Figure 4).
Notably, 5% of the population reported they did not seek medical
attention. Rather, their diagnosis was an incidental finding upon
routine pelvic examination. Sixty-six percent of respondents received an
alternate diagnosis for their genital symptoms before their biopsy
proven diagnosis of LS, with 49% being diagnosed with a vulvovaginal
yeast infection. Other alternative diagnoses included bacterial
vaginosis (23%), overactive pelvic floor dysfunction (6%), genital HSV
infection (4%), atopic dermatitis (3%), estrogen deficiency (3%),
vitiligo (2%), genital psoriasis (2%), lichen simplex chronicus (2%),
lichen planus (1%), and scleroderma (0.2%) (Table 5).
There was an increased incidence of hypothyroidism of 10.1% among
individuals with LS, significantly increased from that of the general
population which is 2.0% (X 2(1, N =503)
= 29.336, p <0.0001). There was also an increased
incidence of vitiligo (2.6% vs 1.0%,X 2(1, N =503) = 12.755, p =0.0004),
pernicious anemia (0.6% vs 0.1%,X 2(1, N =503) = 12.408, p =0.0004),
and celiac disease (2.8% vs 1.4%,X 2(1, N =503) = 6.97, p =0.008) in
those with LS with respect to the general population (Table 6).
DISCUSSION
Main Findings
This cross-sectional web-based study characterized the presenting
symptoms of over 500 premenopausal women with biopsy-confirmed vulvar
LS. Most prevalent and bothersome symptoms in premenopausal women were
dyspareunia and tearing with vaginal insertion, which were more commonly
reported than vulvar itch. Two-thirds of respondents were initially
misdiagnosed, most commonly with vulvovaginal yeast infection, leading
to an average 4-year delay in diagnosis. There is an increased incidence
of hypothyroidism, vitiligo, pernicious anemia, and celiac disease with
vulvar LS in this population.
Strengths and Limitations
There are inherent limitations in an observational web-based study
relying on survey data and self-report. However, this study was able to
recruit a large cohort of premenopausal women with vulvar LS. In order
to increase accuracy in diagnosis, only respondents with
biopsy-confirmed LS were included in the current analysis. Respondents
were from all over the world, although the location of the participants
was not recorded. Due to the low prevalence of vulvar LS in the general
population, it would be difficult to collect this type of cohort through
individual medical practices. Of note, non-white ethnicities where not
well represented in this sample, with less than 1% of respondents
identifying as black. In general, black ethnicities tend to be
under-represented in web-based surveys.18 In the
literature, LS seems more common in white ethnicities; however, this may
be due to reporting bias in epidemiologic studies.19
Interpretation
LS is historically known to have a bimodal distribution, affecting
premenarchial girls and postmenopausal women, and largely sparing those
of reproductive age.20 However, this study recruited
956 premenopausal respondents with vulvar LS, approximately half with
biopsy-confirmed disease and the other half with clinical disease alone.
This not only confirms that LS does indeed affect females of all ages,
but also that rates in reproductive-aged women may be higher than
initially thought. In the literature, up to 40% of women with LS noted
onset of symptoms prior to menopause.1,10 In a
gynecology practice with providers specializing in LS, 46% of the
cohort identified with LS during routine gynecologic examination were
premenopausal, and 39% of those patients were asymptomatic at the time
of diagnosis.2 This raises the question if the bimodal
peak incidence is actually detection bias in
diagnosis.9
Vulvar pruritis is the most commonly cited and widely described
presenting symptom in vulvar LS,20-22 noted to be
present in 98% of women with biopsy-proven LS (average age 54) in one
study.22 However, most of the literature describing
vulvar LS includes predominantly postmenopausal
women.6,10,21-24 In the current study, the most
prevalent symptoms in premenopausal women were related to sexual
function and pain, including dyspareunia, tearing with intercourse or
vaginal insertion, and decreased clitoral sensation. Sexual pain
symptoms were not only most commonly reported, but also most bothersome
and prompted medical attention. Interestingly, decreased clitoral
sensation was not reported to be bothersome or prompt medical attention.
However, vulvar pruritis did prompt medical attention, even though it
was not one of the most common symptoms.
In the present study, vulvar fissures were noted to be a common skin
change that both affected the individual the most and prompted medical
evaluation. Because vulvar pruritis is a well-known and accepted symptom
of vaginitis and vulvar fissures can be associated with vulvar yeast, it
is not surprising that 66% of respondents received an alternate
diagnosis, half of which were misdiagnosed with vulvovaginal yeast
infection and over a quarter with bacterial vaginosis. The current study
found an average delay in diagnosis of 4 years. This is consistent with
previous research, with a mean delay of diagnosis of 4.6 years in a
cohort of girls and women of all ages with vulvar LS ranging from 1-86
years.10 Misdiagnosis and delay in diagnosis may
reflect insufficient training in identifying vulvar dermatoses. A recent
survey of gynecology trainees indicated that they do not feel adequately
trained in vulvar disease, including anogenital LS.25
Five percent of respondents reported that their condition was found
incidentally on gynecologic examination. Studies report a 9% rate of
asymptomatic LS as an incidental finding, but this is in all
ages.19 Goldstein et al. reported that 39% of
asymptomatic women (46% premenopausal) were diagnosed with vulvar LS
incidentally on routine gynecologic examination by practitioners skilled
in diagnosing vulvar dermatoses.2 In the present
study, participants were recruited from social media groups focusing on
the condition. It is likely that those women who are asymptomatic would
be less likely to be present in these groups and less likely to engage
in the study, possibly accounting for a lower rate of asymptomatic
disease at diagnosis in this cohort.
Although decreased levels of estrogen and testosterone have not been
shown to cause lichen sclerosus, it is possible that reproductive
hormones may play a role in symptomatology. Gunthert et al. conducted a
retrospective cohort study comparing 40 premenopausal women with vulvar
LS compared to 100 controls with no vulvar skin condition. The authors
noted all of the women with LS were using oral contraceptive pills,
compared to 66% use in the control group. Specifically, they found that
use of anti-androgenic birth control pills was associated with a 2.5
increased risk of early onset LS. The authors concluded that
anti-androgenic birth control pills could be a cause involved in
LS.8 However, the most recent data favors autoimmune
and genetic etiologies for anogential LS.26 It is
possible that those with LS have a genetic predisposition, thus
decreasing estrogen and androgen levels “uncover” or worsen symptoms
of vulvar LS, namely vulvar pruritis. This would explain why vulvar LS
may be more symptomatic when estrogen levels are low prior to puberty,
seem to improve or disappear in many women during the reproductive
years, but then become more prevalent in menopause, when estrogen levels
decline.
Supporting an autoimmune etiology, it is known that LS is associated
with other autoimmune conditions. The current study found an increased
incidence of hypothyroidism, vitiligo, pernicious anemia, and celiac
disease compared to population data. There was a 10% rate of
hypothyroidism in the study population, compared to a reported rate of
autoimmune thyroiditis of 12-15% in two previously studied
cohorts.27,28 These studies included women of all
ages. Incidence of thyroid disease increases with age, which supports a
slightly lower rate found in our study population. Although celiac
disease is not commonly cited as an associated autoimmune condition with
LS, there has been a recent case report describing anogenital LS in
three premenarchal girls with celiac disease29 and one
report of a 53 year-old women with extragenital LS and celiac
disease.30 Although this has not been explored in the
literature, many patients with vulvar LS find that a gluten-free diet
improves their symptoms. More research is necessary to determine if
there is an association between celiac disease or gluten sensitivity and
vulvar LS and how diet can affect LS symptomatology.
CONCLUSION
Although previous studies have included women of reproductive age,
samples are typically skewed in the postmenopausal range, which adds
caution in generalizing data on symptom presentation and diagnosis to
younger women. Based on current findings, it is necessary to screen
women of all ages who present with sexual pain and tearing at the
introitus for vulvar LS. When first-line treatments for vulvovaginal
yeast infection are not effective and skin changes of the vulva are
present, LS should be considered, especially in premenopausal women.
Acknowledgements: We would like to thank the Lichen Sclerosus Support
Network for supporting our efforts in recruitment on social media.
Disclosure of Interests:
Jill Krapf: Dr. Krapf is a consultant for Mahana Therapeutics and Good
Clean Love.
Andrew Goldstein: Dr. Goldstein is President of the Gynecologic Cancer
Research Foundation, a 501 c3 non-profit corporation, which provided
partial funding for this study. He is a part-time employee of Dare
Bioscience. He has received research funding from Dare Science, SST,
Endoceutics, The Cellular Medicine Association, and Ipsen. He is a
consultant for Ipsen, SST, and AMAG
Alyssa Smith: no disclosures
Sarah Cigna: no disclosures
Contribution to Authorship
JMK: conception, planning, carrying out, analyzing, writing up of the
work; AS: planning, analyzing, writing up of the work; SC: planning,
carrying out, analyzing, writing up of the work: AG: conception,
planning, carrying out, writing up of the work.
Details of Ethical Approval: This study was approved by The George
Washington University Institutional Review Board, #NCR202909.
Funding: none
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Table/Figure Captions
Figure 1: Flow chart of participant inclusion and exclusion criteria.
Figure 2: Time to diagnosed by age of symptom onset.
Figure 3: Number of participants reporting symptoms of decreased
clitoral sensation, dyspareunia, tearing with intercourse or vaginal
insertion, pruritis, and soreness/pain/tenderness based upon symptoms
experienced, symptoms promoting medical evaluation, and symptoms that
affected the individual the most.
Figure 4: Number of participants reporting vulvar architectural or
pigment changes of hypopigmentation, labial resorption, clitoral
phimosis, vulvar fissures, and vaginal stenosis based upon symptoms
experienced, symptoms promoting medical evaluation, and symptoms that
affected the individual the most.
Table 1: Demographics of the study population, including age, ethnicity,
and education.
Table 2: Age at symptom onset and time to diagnosis. *non-numerical
responses were excluded.
There is an inverse correlation between the age at which symptoms began
and the time interval to diagnosis with a Pearson correlation
coefficient of -0.487 (t (455)=14.184, p <.0001.
Table 3: Symptoms experienced, symptoms prompting medical evaluation,
and symptoms that affected the individual most
Table 4: Architectural or pigmentation changes experienced, prompting
medical evaluation, and those that affected the individual most
Table 5: Patient-reported initial alternative diagnoses for their
genital symptoms.
Table 6: Patient-reported coexisting autoimmune disorders diagnosed and
prevalence of these disorders in the general population based upon
reported literature.