ORIGINAL ARTICLE

Lichen planus affecting the female

genitalia: A retrospective review of
patients at Mayo Clinic
Caoimhe M. R. Fahy, MB, PhD, Rochelle R. Torgerson, MD, PhD, and Mark D. P. Davis, MD
Rochester, Minnesota

Background: Genital or vulval lichen planus (VLP) may have a disabling effect on a patient’s quality of
life. Evidence-based management guidelines are lacking for VLP.

Objective: We sought to review clinical presentation and treatment of patients who received a diagnosis of
VLP.

Methods: The 100 consecutive patients who received a diagnosis of VLP at Mayo Clinic between January 1,
1997, and December 31, 2015, were reviewed retrospectively. Descriptive statistics were used for data
analysis. Fisher’s exact test and the Wilcoxon rank sum test were used for analysis of categorical and
continuous variables, respectively. All statistical tests were 2 sided, with the a level set at .05 for statistical
significance.

Results: The time to diagnosis for 49% of patients was more than 1 year. Three patients (3%) had vulval
dysplasia, including invasive squamous cell carcinoma. Sixty-eight patients (68%) had multisite lichen
planus disease. Eleven patients (11%) had disease remission. Dermatology was the lead specialty for 9 of
these cases of remission.

Limitations: This was a retrospective, small-cohort study.

Conclusion: A low frequency of disease remission was seen in patients with VLP. Patients with
lichen planus benefit considerably from dermatology consultation. Further research is warranted to
establish high-quality, evidence-based guidelines for multidisciplinary management of this challenging
disease. ( J Am Acad Dermatol http://dx.doi.org/10.1016/j.jaad.2017.07.030.)

Key words: genital; gynecology; lichen planus; mucosal; therapeutics; vulvar.

L ichen planus (LP) is a chronic inflammatory

dermatosis that affects the skin, mucous
membranes, and nails. The frequency of
vulval involvement has not been established.1 A
Abbreviations used:
LP:
SCC:
SNP:
lichen planus
squamous cell carcinoma
single-nucleotide polymorphism
multidisciplinary vulval clinic study highlighted a VLP: vulval lichen planus
prevalence of 3.7% for biopsy-proven vulval
LP (VLP).2 One study of oral LP reported a biopsy-
proven VLP prevalence of 57%. This is similar to the The cause of LP is not completely established.4,5
prevalence in earlier work with oral LP and Multiple etiologic factors are likely, with autoimmune
cutaneous LP, in which 51% of study patients also associations featuring strongly. T-cellemediated
had VLP.1,3 autoimmune inflammation may be important in the

From the Department of Dermatology, Mayo Clinic, Rochester.
Supported in part by a grant from The City of Dublin Skin and
Cancer Hospital Charity (to Dr Fahy).
Conflicts of interest: None declared.
Accepted for publication July 13, 2017.
Reprint requests: Mark D. P. Davis, MD, Department of Dermatology,
Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail: davis.
mark2@mayo.edu.
Published online October 11, 2017.
0190-9622/$36.00
Ó 2017 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2017.07.030

1
2 Fahy, Torgerson, and Davis J AM ACAD DERMATOL
n 2017

cause, with T cells homing to basal keratinocytes.6,7 plan in VLP can lead to significant reductions in
In LP, a genetic predisposition may allow measures of symptoms, disease lesions, and pain.23
triggering of unidentified self-antigens or exogenous
antigens.6,8 A recent phenome-wide association METHODS AND MATERIALS
study illustrated that LP had associations with major The Mayo Clinic Institutional Review Board
histocompatibility complex single-nucleotide poly- approved the present study. The cases of 100 consec-
morphisms (SNPs), including a genome-wide associ- utive female patients with biopsy-proven VLP from
ation with SNP rs1794275. January 1, 1997, to December
This SNP is also associated 31, 2015, were reviewed.
with other autoimmune dis- CAPSULE SUMMARY
Dermatologists, gynecolo-
orders.8 Antibasement mem- gists, and dermatopathologists
d Vulval lichen planus (VLP) is a chronic
brane zone antibodies made clinical diagnoses. A
inflammatory mucocutaneous disorder
targeting BP180 have been retrospective chart review
associated with severe pain and impact
found in 61% of patients.6 used the institutional elec-
on quality of life.
A controlled observational tronic health record system
study showed that 29% of d For the majority of patients with VLP,
for women age 18 years or
patients with VLP had 1 or current therapeutic options do not lead
older with VLP. Subtypes of LP
more autoimmune diseases.7 to adequate improvement of disease.
were not part of the data
Autoimmune disease was d Development of diagnosis and sought in the electronic record
more frequent in patients management guidelines of VLP is interrogation. Variables
with VLP than in control necessary. included clinical characteris-
patients.7,9 tics, laboratory data, specialty
Over the past 20 years, practitioners involved, admin-
studies have demonstrated that more than 50% of istered treatments, and treatment responses. Disease
women with oral or cutaneous LP also had signs of remission was defined as continued lack of clinical
VLP.1,9 LP has a number of subtypes, including activity in genital mucosa, without regular use of
classical, erosive/mucosal, hypertrophic, lichen prescribed medication.
planopilaris, and mixed. Vulvovaginogingival Descriptive statistics for categorical variables are
syndrome is a subtype of LP in which disease affects reported as frequency and percentage, continuous
the vulva, vagina, and gingival margins.10 Clinical variables as mean (standard deviation) and median
follow-up is necessary because of relapse. Mucosal (range). Categorical variables were compared
LP may result in scarring if it is not recognized and between the patient cohorts with and without
treated.10 A person with vulvovaginogingival disease remission through Fisher’s exact test.
syndrome is at increased risk for vulvar squamous Continuous variables were compared using the
cell carcinoma (SCC), although the exact rates are Wilcoxon rank sum test. Statistical tests were 2-sided
unknown.11,12 A study of LP-associated vulval SCC with the a level set at .05 for statistical significance.
showed that such a cancer, arising in nonhairy vulval
mucosa, had a high frequency of inguinal metastases
at presentation and a high rate of recurrence in the RESULTS
11
residual diseased mucosa. Oral LP is considered a The 100 consecutive study patients first presented
premalignant lesion with a prevalence of malignant to Mayo Clinic from 1997 through 2015. Table I
transformation between 0% and 10%. 13 summarizes study cohort characteristics.
A Cochrane systematic review established that no
randomized controlled trial involving VLP had been Clinical presentation
reported.14 Since then, a randomized controlled trial Table II shows results of whether the dermatology
demonstrated that topical photodynamic therapy service was involved in the patient’s care, length of
was effective and safe for treating VLP.15 clinical follow-up, sites of disease, and whether
Management of VLP is varied and without disease systemic therapy was used.
remission for the majority of patients.16,17 It has been Ninety-one patients could determine the duration
acknowledged that therapeutic options for VLP need of their symptoms of VLP. The median time to
to be broadened, with the development of diagnosis from symptom onset was 12 months
specific measures for diagnosis and management (range, 1-540 months). Four patients self-reported
guidelines.18-21 Nine diagnostic criteria for erosive that they had had symptoms for ‘‘years.’’ Five other
VLP were established through international expert patients were unsure of the duration of their
consensus (Fig 1).22 Use of a standardized treatment symptoms, which were mild or not perceived, and
J AM ACAD DERMATOL Fahy, Torgerson, and Davis 3
VOLUME jj, NUMBER j

Fig 1. Diagnosis of vulval lichen planus. A, Lichen planus affecting the vulval mucosa. The
image shows glazed erythema at the vaginal introitus (red arrow), a hyperkeratotic white
border to the erythematous area (yellow arrow), and evidence of mucosal scarring and loss of
normal architecture indicated (thin yellow lines). B, The 9 criteria established by international
consensus of experts on vulval disease at an international electronic-Delphi consensus
exercise. At least 3 of the 9 criteria must be present for diagnosis of vulval erosive lichen
planus. (Adapted from Simpson et al.22 Used with permission.)

1 patient had symptoms for up to 50 years before
diagnosis.
Most patients had LP that affected multiple sites
(Tables I and II). One of the 4 patients with
esophageal LP was referred to the dermatology
service for assessment of genital symptoms. The
other 3 patients received a diagnosis because
symptoms of esophageal disease were noted at
dermatology review.
and potent topical corticosteroids, 33 (75%) needed
superpotent topical corticosteroid to improve
disease control.
When disease control was not adequately
achieved despite diligent use of appropriate topical
treatments, 43 patients (43%) received systemic
medication. Two patients had improved VLP
secondary to intravenous IgG treatment.

Dermatopathologic results Disease clearance

All patients had a genital biopsy reviewed by a
dermatopathologist, confirming the diagnosis of
VLP. Features noted in the histopathologic
assessment are detailed in Table III. Important
diagnostic features for VLP include lichenoid
infiltration at the dermatoepidermal junction and
epidermal thickening. Two-thirds of the patients
required 1 biopsy; 27 had multiple biopsies.
Immunofluorescence was performed on 36 biopsy
specimens. In 22 specimens, shaggy deposition of
fibrogen was seen on the basement membrane area,
which is histopathologically typical of LP.
Disease management
Table IV outlines disease management. Topical
emollients and over-the-counter preparations were a
basic part of maintenance treatment. Of the 47
patients (47%) who initially used mild, moderate,
Seventy-nine study patients (79%) were
monitored for a median of 24 months (range,
1 week to 165 months). Table V shows analysis of
disease outcome in relation to a number of variables.
Patients who did not have remission were
observed in clinical care for a mean of 42 months
(median, 36; range, 0.3-165). Latest disease status
was unknown for 12 patients. Of the patients with
remission, 2 with solely VLP received treatment with
superpotent topical corticosteroid only, whereas a
third patient with solely VLP had adequate disease
remission with moderate topical corticosteroid only.
Of 3 patients with vulvovaginal disease, 1 had
adequate disease remission while taking
superpotent topical corticosteroid. The second
patient required a moderate and then a superpotent
topical corticosteroid for disease remission. The third
patient had more complex disease, requiring
4 Fahy, Torgerson, and Davis J AM ACAD DERMATOL
n 2017

Table I. Characteristics of 100 consecutive female Table II. Management of vulval LP for 100
patients presenting with vulval LP consecutive patients
Characteristic Value* Management Value*
Age at diagnosis, y Dermatology as first specialty
Mean (SD) 60.3 (12.3) No 37 (37)
Median 62.5 Yes 63 (63)
IQR 52.0-69.0 Dermatology involved
Range 27.0-89.0 No 10 (10)
Specialty at presentation Yes 90 (90)
Dermatology 63 (63) Follow-up, mo 81
Gynecology 33 (33) Mean (SD) 39.5 (41.0)
Family practice 2 (2) Median (range) 24.0 (0.3-165.0)
Internal medicine 1 (1) Multiple areas involved
Gastroenterology 1 (1) No 31 (31)
Specialty of referral Yes 69 (69)
Dermatology 27 (27) Systemic therapy used
Gynecology 3 (3) No 57 (57)
NA 70 (70) Yes 43 (43)
Time to diagnosis (categorical), y
Uncertain 5 (5) LP, Lichen planus; SD, standard deviation.
\1 46 (46) *Values are reported as number and percentage of patients unless
1-3 13 (13) specified otherwise.
4-5 17 (17)
5-10 11 (11) Table III. Dermatopathologic finding for skin
[10 8 (8)
biopsies in vulval LP of 100 consecutive patients
Site of LP disease
Vulval mucosa 100 (100) Dermatopathologic finding No. of specimens
Vulval mucosa only 31 (31) Mucosal biopsy 117
Oropharyngeal mucosa 47 (47) Bandlike infiltrate at DEJ 102
Vaginal mucosa 46 (46) Foci of lichenoid inflammation 116
Esophageal mucosa 4 (4) Lichenoid mucositis 117
Ocular mucosa 2 (2) Interface dermatitis 93
Skin 20 (20) Thickened epidermis 11
Scalp 11 (11) Effaced epidermis 2
Disease symptoms Plasma cell infiltrate 5
Dyspareunia 91 (91) Lymphocytic infiltrate 21
Pain, burning sensation, pruritus 69 (69) Eosinophils 15
Burning sensation, pruritus 8 (8) Parakeratosis 2
Pain 7 (7) Cytoid bodies 1
Pruritus 4 (4) Granular zone accentuation 2
Pain, pruritus 2 (2) Nonspecific inflammation 7
Family history of LP 2 (2)
Autoimmune disease 22 (22) DEJ, Dermoepidermal junction; LP, lichen planus.
Thyroid disease 17 (17)
Vitiligo 1 (1)
Rheumatoid arthritis 1 (1) methotrexate. The other patient received a super-
Celiac disease 1 (1) potent topical corticosteroid and acitretin before
Family history of autoimmune disease 5 (5) changing systemic therapy to methotrexate.
One patient, who had many affected sites and VLP
IQR, Interquartile range; LP, lichen planus; NA, not referred to other
specialties; SD, standard deviation.
remission, had used a superpotent topical
*Values are reported as number and percentage of patients unless corticosteroid to control cutaneous, oral, and
specified otherwise. vulvovaginal LP. A patient with more complex
disease involving the vulvovaginal, oral, and
a superpotent topical corticosteroid, topical esophageal mucosa achieved VLP remission with a
tacrolimus, and cephalexin. superpotent topical corticosteroid, tacrolimus, and
Two patients with vulvovaginal and oropharyngeal mycophenolate mofetil. The final patient with VLP
LP had VLP remission. One required superpotent remission had LP affecting the skin; the scalp; and the
topical corticosteroids, oral corticosteroids, and then ocular, oropharyngeal, and vulvovaginal mucosa.
J AM ACAD DERMATOL Fahy, Torgerson, and Davis 5
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Table IV. Treatments of vulval LP for 100 combinations of oral antibacterial and antifungal
consecutive patients therapies.
Disease management Patients, n (%)
We hypothesized that a patient may have an
increased chance of VLP remission when the
Nonprescription topical therapy 37 (37)
specialty of dermatology is involved in patient care.
Emollients 18 (48.6)
Acetic acid soaks 11 (29.7) Although statistical significance was not achieved, 9
Zinc oxide 8 (21.6) of 11 patients with VLP remission (82%) were
Prescribed topical therapy receiving care through the dermatology service. By
Topical local anesthetic 10 (10) comparison, 4 of 6 patients not seen by the
Corticosteroids 95 (95) dermatology service (66%) did not have VLP
Mild 17 (17.9) remission (P = .26).
Moderate 24 (25.3) More than 50% of patients had involvement and
Potent 19 (20.0) combinations of mucosal, cutaneous, and scalp
Superpotent 44 (46.3) disease. Patients who achieved disease remission
Vaginal suppositories 9 (9.5)
tended to have multiple areas of involvement. Most
Required increasing potency of corti- 33 (34.7)
patients who received systemic treatments did not
costeroid to superpotent level
Calcineurin inhibitors 56 (56) achieve VLP remission. Of the patients with disease
Tacrolimus 45 (80.4) remission, approximately one-half were prescribed
Pimecrolimus 11 (19.6) systemic medications.
Combination topical therapy 43 (43)
Tacrolimus and clobetasol 35 (81.4) Disease sequelae
Pimecrolimus and clobetasol 8 (18.6) Three patients had vulval dysplasiad1 with SCC
Systemic therapy 43 (43) in situ and 2 with invasive vulval SCC.
Antibiotic courses (ie, metronidazole, 16 (37.2) Histopathologic analysis of these lesions commented
cephalexin, or a combination on background features of LP. In 1 patient, topical
of amoxicillin and clavulanic acid
corticosteroideinduced mucosal or cutaneous
[co-amoxiclav])
atrophy developed. One patient had burning
Antifungal oral treatments 14 (32.6)
Acitretin 1 (2.3) sensations from topical corticosteroid preparations,
Isotretinoin 3 (7.0) and 1 patient had diabetes mellitus and myositis
Hydroxychloroquine 12 (27.9) induced by oral corticosteroid therapy.
Dapsone 3 (7.0)
Colchicine 1 (2.3) DISCUSSION
Oral corticosteroids 22 (51.2) This study enabled a retrospective review of
Methotrexate 17 (39.5) consecutive patients assessed at a tertiary referral
Mycophenolate mofetil 10 (23.3) center with expertise in vulval dermatoses. Similar to
Azathioprine 5 (11.6) previous reports,16 this review had a majority of
Cyclosporine 4 (9.3)
white patients. Mean age at diagnosis in the present
Intravenous IgG 2 (4.7)
review was similar to the average age of affected
LP, Lichen planus. patients in other studies.2,16
The mucosal immune system is complex, deals
She required treatment with mild, potent, and with various antigenic exposures, and becomes
superpotent topical corticosteroids. She then compromised with aging.24 In the genetically
required systemic medications, including acitretin, susceptible person, mucosal immunosenescence
isotretinoin, metronidazole, antifungal therapies, may result in development of mucosal LP. This may
and immunosuppression with methotrexate. In this be related to age at onset of VLP, in comparison with
final case, intravenous IgG allowed a full VLP the peaks in age at lichen sclerosus onset. The
response. association of autoimmune disease in this study
Of the 77 patients with confirmed disease (22%) is notable.
persistence, 10 patients with only VLP had at least 1 The potential for an extended period of symptoms
form of systemic treatments, which included oral before diagnosis was highlighted by this study. The
corticosteroids (n = 3); acitretin, then mycophenolate median time in our data was 12 months. Among
mofetil, and then cyclosporin after a course of oral patients, 40% had a VLP diagnosis within 1 year of
corticosteroids (n = 1); and hydroxychloroquine symptom onset. A large proportion of patients had
after oral corticosteroids (n = 3). Two patients with poorly controlled disease because of factors that
VLP had methotrexate only; 5 patients had included delayed clinical presentation owing to lack
6 Fahy, Torgerson, and Davis J AM ACAD DERMATOL
n 2017

Table V. Disease remission of 100 consecutive patients with diagnosis of vulval LP

Remission*
Case-specific variable No (n = 77) Yes (n = 11) P valuey
Dermatology as first specialty .74z
No 29 (37.7) 5 (45.5)
Yes 48 (62.3) 6 (54.5)
Dermatology specialty involved .26z
No 6 (7.8) 2 (18.2)
Yes 71 (92.2) 9 (81.8)
Follow-up, mo .32x
No. of patients 67 10
Mean (SD) 42.7 (40.3) 32.9 (48.5)
Median (range) 36.0 (0.3-165.0) 12.0 (1.0-159.0)
Multiple areas involved [.99z
No 25 (32.5) 3 (27.3)
Yes 52 (67.5) 8 (72.7)
Systemic therapy used [.99z
No 43 (55.8) 6 (54.5)
Yes 34 (44.2) 5 (45.5)

LP, Lichen planus; SD, standard deviation.

*Values are presented as number and percentage of patients unless specified otherwise.
y
All statistical tests were 2 sided, with the a level set at .05 for statistical significance.
z
Categorical variables were compared between patients with and without disease remission by using Fisher’s exact test.
x
Continuous variables were compared by using the Wilcoxon rank sum test.

of understanding or embarrassment, as well as absence of evidence-based management guidelines.

inadequate treatment or delayed diagnosis of VLP.
This study explored that the idea VLP-induced
pain considerably affects a patient’s quality of life.
Chronic pain in LP is associated with increased risk
for anxiety, stress, and depression.25 Patients with
inflammatory skin disorders associate some flares in
pain and disease with times of stress.26,27 Use of a
validated pain score and a quality of life score when
evaluating VLP will help monitor disease. These
scoring systems may then be comparable across
clinical centers.
Most patients with a diagnosis of VLP have had a
tissue biopsy, although accurate clinical diagnoses
are possible. The histopathologic features of LP and
early lichen sclerosus can overlap.21 Plasma cell
infiltration tends to be seen in mucosal LP more
than in the other LP types.28 Vaginal involvement in
lichen sclerosus is rare.21
Analysis of disease management in the present
study further emphasized that VLP is a challenging
inflammatory disease. Although management was in
line with reported usual treatments for VLP, 11% of
affected patients in this study had disease remission.
Three of these patients (3%) had VLP solely, and
topical corticosteroids achieved remission. However,
28 other patients with VLP solely (28%) did not
achieve disease remission. Less than 50% of patients
in this study had systemic medication. Hesitancy
about systemic treatment may originate in the
This may confirm previous suggestions that mucosal
LP requires a management approach similar to that
with a systemic disease.19 Disease improvement
with topical therapy in this study was usually the
result of counseling by the treating clinician. A
further study on topical treatment compliance in
VLP may highlight areas for optimization of disease
management.
This study highlighted the importance of the
dermatology service being involved in manage-
ment of VLP. Referral to the dermatology service
for review of LP with a genital examination is
essential, considering that more than one-half of
patients with oral or cutaneous LP have signs of
VLP.1 The development of vulval dysplasia in this
study (n = 3 [3%]) indicates that VLP requires
adequate clinical follow-up. Adverse effects of
treatment may result in serious comorbidity, as
found in this study.
Limitations of the present study include its
retrospective cohort review of a small number of
patients. Selection bias was avoided by including
only consecutive cases with a clinicodermatopatho-
logic diagnosis. Referral bias may exist, causing a
reduced variation in diagnoses. These results may
not apply to other populations because we are
reporting data acquired at a single tertiary care
center. Other long-term consequences of VLP may
have occurred without the knowledge of
J AM ACAD DERMATOL
VOLUME jj, NUMBER j
investigators because patient follow-up was only for
a median of 24 months.
This study, like previous reports on VLP, suggests
that the use of standardized, evidence-based
guidelines on diagnosis, management, and
treatments increases the potential for inflammatory
disease remission. Quality of life for a patient should
thus also be improved. Further laboratory and
clinical research into molecular aspects and
treatment of mucosal LP may allow the development
of new therapeutic options.
We thank Zhuo Li and George M. Cooper, Health
Science Research, Mayo Clinic, Jacksonville, Florida, for
their assistance with statistical analysis.
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