Diagnosis and Treatment of Lichen Sclerosus
Susanna K. Fistarol•Peter H. Itin
Published online: 14 December 2012
? The Author(s) 2012. This article is published with open access at Springerlink.com
mucocutaneous disorder of genital and extragenital skin. LS
is a debilitating disease, causing itch, pain, dysuria and
restriction of micturition, dyspareunia, and significant sexual
dysfunction in women and men. Many findings obtained in
recent years point more and more towards an autoimmune-
induced disease in genetically predisposed patients and fur-
ther away from an important impact of hormonal factors.
Preceding infections may play a provocative part. The role
for Borrelia is still controversial. Trauma and an occlusive
moist environment may act as precipitating factors. Potent
and ultrapotent topical corticosteroids still head the thera-
peutic armamentarium. Topical calcineurin inhibitors are
discussed as alternatives in the treatment of LS in patients
who have failed therapy with ultrapotent corticosteroids, or
who have a contraindication for the use of corticosteroids.
Topical and systemic retinoids may be useful in selected
cases. Phototherapy for extragenital LS and photodynamic
therapy for genital LS may be therapeutic options in rare
cases refractory to the already mentioned treatment. Surgery
is restricted to scarring processes leading to functional
impairment. In men, circumcision is effective in the majority
ofcases,but recurrences are well described.AnogenitalLS is
associated with an increased risk for squamous cell carci-
noma of the vulva or penis. This review updates the epide-
miology, clinical presentation, histopathology, pathogenesis,
and management of LS of the female and male genitals and
extragenital LS in adults and children.
Lichen sclerosus (LS) was described for the first time in
1887. Since then, many synonyms have been in use,
notably ‘Kraurosis vulvae,’ ‘vulvar dystrophy,’ ‘white
spot disease,’ and ‘lichen sclerosus et atrophicus’ or
‘guttate scleroderma.’ All of these terms have been
abandoned and replaced by ‘lichen sclerosus,’ which is
now used for genital and extragenital lesions. LS is a
chronically relapsing disease with a potential for atrophy,
destructive scarring, functional impairment, and malignant
evolution. Therefore, early diagnosis, prompt treatment,
and long-term follow-up of affected patients are manda-
tory. Spontaneous remissions are rare. LS can not be
cured, but can be controlled by adequate treatment. With
early treatment, long-term sequelae such as destruction of
anatomic structures and progression to squamous cell
carcinoma (SCC) may be prevented. For the affected
patients it is essential that dermatologists, gynecologists,
urologists, histopathologists, surgeons, general practitio-
ners, and pediatricians, respectively, have a solid knowl-
edge of the disease and will not hesitate to cooperate
if required. Since LS begins with uncharacteristic symp-
toms, a meticulous clinical examination, raising the
clinical suspicion and, if necessary, a histopathologic
confirmation is required.
We searched MEDLINE for relevant papers from 2004
to 2011 using the terms ‘lichen sclerosus’ or ‘balanitis
xerotica obliterans’ in association with ‘epidemiology,’
‘infection,’ ‘borrelia,’ ‘children,’ ‘extragenital,’ ‘steroid,’
‘pimecrolimus,’ ‘tacrolimus,’ ‘testosterone,’ ‘retinoid,’
‘UVA1,’ ‘UVB,’ ‘photodynamic therapy,’ ‘malignancy,’
or ‘squamous cell carcinoma.’ The MEDLINE search for
‘lichen sclerosus’ alone produced 1524 citations.
S. K. Fistarol ? P. H. Itin (&)
Department of Dermatology, University Hospital Basel,
Petersgraben 4, 4031 Basel, Switzerland
S. K. Fistarol
Am J Clin Dermatol (2013) 14:27–47
LS is a chronic, inflammatory skin disease with a distinct
predilection for the anogenital region. Only 6 % of LS are
isolated extragenital lesions . Oral LS has rarely been
described [2–4]. The exact prevalence of LS is difficult to
ascertain and probably underestimated, since patients with
LS may present to various clinical specialities, physicians
do not always recognize LS, and patients may not report
symptoms because of embarrassment or because they are
asymptomatic . However, in 1971, Wallace  calcu-
lated a prevalence of 0.1–0.3 % of all patients referred to a
community-based dermatology department. Both female
and male patients are affected and it occurs in children, and
in adults. The disease may occur for the first time at any
age. There is a typical bimodal onset in prepubertal chil-
dren and in postmenopausal women, respectively, and in
men in their fourth decade. Affected female patients clearly
outnumber male patients.
Goldstein et al.  found a prevalence of vulvar LS in a
general gynecology practice of 1.7 %. Powell and Wo-
jnarowska  found a prevalence of LS in premenarchal
girls of 0.1 %. Kizer et al.  studied a population of
153,432 male patients and found that 0.07 % had a diag-
nosis of LS. Nelson and Peterson  recently calculated in
a population of 42,648,923 male patients a prevalence of
only 0.0014 %.
3 Disease Pathogenesis
The etiology of LS has not yet been adequately explained,
but there is increasing evidence that autoimmune mecha-
nisms play a pathogenetic role. There appears to be a
genetic susceptibility to LS. The chronic irritant effects of
urinary contact are suggested to be provocative. No
infectious agent has been consistently linked to LS.
In common with many autoimmune diseases, LS is more
prevalent in female patients. A large study of 350 women
with LS revealed that 21.5 % had one or more autoim-
mune-related diseases, 21 % had a family history of
autoimmune disease, and 42 % had autoimmune antibodies
. The most common autoimmune diseases in this group
were autoimmune thyroiditis (12 %), alopecia areata (9 %),
vitiligo (6 %), and pernicious anemia (2 %). These disor-
ders should be considered in patients with LS . In a LS
cohort of 190 women, Cooper et al.  found 28 % had
one or more associated autoimmune diseases compared
with 9 % of 230 control patients. Thyroid disease was the
most prevalent autoimmune disorder occurring in 16 % of
the LS cohort versus 8 % of controls. Birenbaum and
Young  found that the prevalence of thyroid disease in
211 women with biopsy-proven LS was 30 %. In com-
parison, in the general population of Scotland, Leese et al.
 observed in 2001 an overall prevalence of thyroid
dysfunction of 3.8 %. Female patients showed a prevalence
of 6.4 % and male patients showed a prevalence of 1.1 %.
In a group of 30 prepubertal girls with anogenital LS,
6.6 % had an associated autoimmune disease (vitiligo and
alopecia areata), and 56 % of their parents or grandparents
In men, the association with autoimmune disease is
weaker. In a study of 35 men with LS, 6 % had an asso-
ciated autoimmune disease and 19 % had a positive family
history for autoimmune disease . Another study
showed that only 3 % of 58 men with LS had a personal
history of autoimmune disease, and 10 % had a first-degree
relative with an autoimmune disease . In a case-control
study, 73 men with LS were compared with 219 controls.
Vitiligo (12 % vs. 0 %) and alopecia areata (12 % vs. 1 %)
were significantly more common in patients than in con-
trols. A family history of diabetes mellitus, vitiligo, alo-
pecia areata, or thyroid disease and the presence of other
autoimmune diseases were identified as risk factors for
male LS .
Circulating IgG autoantibodies targeting extracellular
matrix 1 (ECM1) protein have been demonstrated in the
sera of 74 % of women with anogenital LS compared with
7 % in controls . ECM1 autoreactivity was more likely
in individuals whose disease duration was greater than
1 year and/or in those with more extensive disease, sug-
gesting that ECM1 autoreactivity might be involved in the
progression rather than in the initiation of the disease. Also,
in men, the anti-ECM1 antibody concentrations were sig-
nificantly higher in men with LS than in controls . The
authors propose that chronic irritation of the genital epi-
thelium may lead to previously sequestered site-specific
skin epitopes being revealed and that those patients with an
autoimmune diathesis would subsequently be more likely
to develop antibodies. They suggest that ECM1 autoim-
munity might be an epiphenomenon rather than being
directly pathogenic . The human ECM1 gene was
isolated in 1997. Since then, several important biologic
functions have been attributed to the glycoprotein ECM1.
Within the epidermis, ECM1 has a role in the control of
keratinocyte differentiation. Within the dermis, ECM1 has
a role in the structural organization of the dermis, binding
to perlecan, matrix metalloproteinase-9, and fibulin. ECM1
helps to regulate basement membrane and interstitial col-
lagen fibril macro-assembly and growth factor binding. It
stimulates proliferation of endothelial cells and induces
angiogenesis. In 2002, loss-of-function mutations in the
ECM1 gene were discovered to cause lipoid proteinosis
28 S. K. Fistarol, P. H. Itin
(OMIM 247100), also known as Urbach-Wiethe disease or
hyalinosis cutis et mucosae, a rare autosomal recessive
genodermatosis, clinically characterized by skin and
mucosal infiltration and scarring, and histologically by
disruption/duplication of the basement membrane and
widespread deposition of hyaline material in the dermis.
ECM1 shows overexpression in certain malignancies and is
abnormally expressed in chronologically aged and photo-
aged skin .
Antibodies targeting the basement membrane zone
(BMZ) [BP180 and BP230] have been found in one-third
of patients with vulval LS . Baldo et al.  demon-
strated that in 43 % of their vulval LS patients the NC16A
domain of BP180 is a target for circulating T cells, and
there are associated autoantibodies to BP180. In girls with
vulvar LS, a prevalence of 45 % (4/9) of circulating BMZ
autoantibodies was found . However, in the most recent
study concerning this topic only 3.4 % of 149 LS patients,
compared with 94.7 % of 38 bullous pemphigoid patients
and 0 % of 36 healthy controls had elevated anti-BMZ
antibodies, producing no significant difference between LS
patients and controls  so that the pathogenetic role of
BMZ antibodies remains uncertain.
3.2 Genetic Factors
A large, observational, cohort study of a total of 1052
women with vulval LS showed that 12 % had a positive
family history of LS , indicating that familial cases of
LS probably have been underreported so far. Patients with
familial LS had more often associated autoimmune disease
(7 %) than patients with sporadic LS (5 %), although this
increase was not statistically significant . A genetic
predisposition seems likely.
Human leukocyte antigen (HLA) DQ7 has been shown
to occur more frequently in both women and men with LS
[15, 17, 27]. HLA DQ8 and DQ9 have been found more
frequently in women with LS than in controls . Asso-
ciations between LS and HLA -B*08–B*18 , -B*15,
-B*57, -CW*03, -CW*07, -CW*18, -DRB1*04, -DRB4*,
-DRB1*07 , -DRB1*12 and the haplotype DRB1*12/
DQB1*0301/04/09/010 have been documented . HLA
DR11 and DR12 were more common in men with LS .
3.3 Trauma and Chronic Irritation
Genital LS is described to occur in patients with genital
jewellery and after surgery, trauma, and instrumentation,
and does recur in grafts and circumcision scars . It is
very uncommon that a man circumscribed at birth will
develop LS. So it seems likely that the occlusive, moist
environment under the prepuce is permissive for the
development of genital LS. Chronic exposure to urine has
been implicated as a causative factor for genital LS
[32, 33]. Edmonds and Bunker  used high-resolution
nuclear magnetic resonance spectroscopy to investigate
potential alterations in urinary constituents in male genital
LS. They identified creatinine, citrate, hippurate, dimeth-
ylamines, trimethylamines, alanine, and bile acids. No
significant differences were found between the urine sam-
ples of men with and without genital LS.
3.4.1 Borrelia burgdorferi
Previous studies based on serologic tests, culture, immu-
nohistochemistry, and polymerase chain reaction (PCR)
reported conflicting results concerning the role of Borrelia
in the pathogenesis of LS. Borrelia species have been
detected in cases from Europe, but not from the USA.
Edmonds et al.  tested sera from 30 adult male
patients with genital LS and from 32 aged-matched con-
trols by IgG Western blotting. All of the LS patients tested
negative and one of the controls had a positive serology.
By immunoperoxidase reaction, Aberer et al. [36, 37]
detected Borrelia burgdorferi in 47 % (7/15) of their LS
patients. Studies from Europe using PCR approaches
revealed positive results ranging from 0 to 100 % [38–46],
taking those studies together positive results were obtained
in this way in 34 % (28/83).
Using focus-floating microscopy (FFM), Borrelia spe-
cies were found in 63 % (38/60) of cases of LS compared
with 90 % of positive controls of classic borreliosis and
0 % of negative controls . In these patients, Borrelia
species were detected significantly more often in early
inflammatory-rich (80 %, 31/39) than in late inflammatory-
poor (33 %, 7/21) cases. Eleven skin biopsies of patients
from the same patient group were also examined by PCR.
Remarkably, none of the 11 samples was positive for
Borrelia by PCR, while 6 of 10 out of the same 11 cases
were positive by FFM , indicating the difficulties of the
various techniques to reliably detect Borrelia in tissue
3.4.2 Epstein-Barr Virus
In a preliminary study, Epstein-Barr virus (EBV) DNA was
found in 26.5 % of 34 vulvar biopsies of patients with LS
compared with 0 % in controls . Future studies have to
elucidate whether EBV actually plays a role in cases of LS.
3.5 Hormonal Influences
Serum levels of dihydrotestosterone were found to be
significantly decreased in patients with untreated vulvar
LS. These results seemed to suggest that decreased
5a-reductase activity was an etiologic factor for LS .
Moreover, immunohistochemical evaluation of andro-
gen receptors in genital and extragenital LS provided evi-
dence for the loss of androgen receptors with disease
progression in lesional skin . Treatment with topical
testosterone in the past, based on those findings, has been
abandoned for lack of evidence for its effectiveness .
Gu ¨nthert et al.  retrospectively analyzed the data of
40 premenopausal patients with early-onset LS in a case-
control study with a matched control group of 110 healthy
women to find potential risk factors for early-onset vulvar
LS focussing on the use of oral contraceptives (OCPs). One
hundred percent of the LS patients were using OCPs
compared with 66.4 % in the control group. OCPs with
antiandrogenic activity were used by 70 % of the LS
patients and by 48 % of the women using OCPs in the
control group, suggesting that disturbance of the androgen-
dependent growth of the vulvar skin by OCPs and espe-
cially by OCPs with antiandrogenic properties might trig-
ger the early onset of LS in a subgroup of susceptible
4 Natural Course
In male and female patients, LS is usually a scarring,
chronic progressive or relapsing and remitting, lifelong
condition. There are few publications referring to the long-
term follow-up of LS patients. Nevertheless, it is well
known that LS in adult women may cause significant
alteration in vulvar architecture. The labia minora may
become reabsorbed and fused, and the clitoris entrapped
under scar tissue. The vaginal introitus may become ste-
notic and narrowed. In men, the frenulum often becomes
contracted and circumferential involvement of the preputial
aperture leads to a progressive fibrous phimosis. The sur-
face of the glans and inner prepuce may ulcerate. Sub-
sequent fibrosis may lead to dense fusion of the layers.
Urethral involvement starts at the meatus. In long-standing
disease, meatal stenosis may progress to involve the entire
length of the urethra spreading proximally as far back as
the prostate .
Less commonly, genital LS may be complicated by
One prospective case series reported on a cohort of 12
girls with prepubertal LS followed up for to 10 years until
adolescence. Twenty-five percent had complete remission,
whereas 75 % remained symptomatic and showed definite
physical signs of LS when examined as adolescents .
Fifty percent of the children experienced distortion in
vulvar architecture, including loss of labia minora and
clitoral substance. A previous study followed 21 girls who
developed LS before puberty examining the clinical course
after puberty . In postpuberty, 52 % still experienced
occasional pruritus, requiring intermittent topical cortico-
steroid application, and definite physical signs persisted in
The diagnosis of LS is usually clinical. When the clinical
features are typical, histologic examination is not always
essential. However, in the early stages of the disease the
diagnosis can be difficult. The main differential diagnoses
are lichen planus (LP), lichen simplex chronicus, vitiligo,
immunobullous disorders such as mucous membrane
pemphigoid and vulvar or penile intraepithelial neoplasia
[11, 54]. In clinically inconclusive cases, a histologic
examination is advisable and might close the gap, but
should never be interpreted in isolation. One-third of men
having sufficient symptoms and signs to be clinically
diagnosed with LS, showed only nonspecific histology on
biopsy or in the circumcised prepuce . A nonspecific
biopsy does not rule out LS, but classic histologic findings
confirm the diagnosis . Patients under routine follow-
up will need a biopsy if: (1) there is a suspicion of neo-
plastic change, i.e., a persistent area of hyperkeratosis,
persistent erosion, or erythema, or new warty or papular
lesions; (2) there is an area resistant to adequate treatment;
(3) there is extragenital LS, with features suggesting an
overlap with morphea; (4) there are pigmented areas, in
order to exclude an abnormal melanocytic proliferation;
and (5) second-line therapy is to be used .
There are instances when it can be impossible to dif-
ferentiate between LS and LP either on the basis of the
clinical or the histologic features (Table 1). These cases are
described as overlap syndrome and often show poor
response to treatment .
5.1 Clinical Features
5.1.1 Female Anogenital Lichen Sclerosus (LS): Adults
typical and histologically confirmed LS. The mean age at
of LS was in prepuberty, in 41 % in the reproductive years,
and in50 % postmenopause. Cooper etal.  studied a total
vulvar LS. Twenty-three percent of the patients were
premenarchal, 17 % in their reproductive years, and 60 %
postmenopausal. The mean age at onset of symptoms was
5.4 yearsforgirlsand55.1 yearsforwomen.Themeanageat
diagnosis was 7.6 years for girls and 60 years for women.
30S. K. Fistarol, P. H. Itin
The area involved may vary from a small, single area
(Fig. 1) to the entire region of vulva, perineum, and peri-
anus. There may be extension to the genitocrural folds,
buttocks, and thighs (Fig. 2). The characteristic sites
involved are the interlabial sulci, labia minora and labia
majora, clitoris and clitoral hood, and perineum and peri-
anal area, giving rise to the characteristic ‘figure-of-eight’
shape (Fig. 3). Genital mucosal involvement does not
occur, the vagina and cervix always being spared, in con-
trast to LP . A retrospective chart review of 81 con-
secutive patients with LS showed that almost all of the
affected women had labial involvement, with concomitant
involvement of the clitoris (70 %), perineum (68 %), and
perianal region (32 %) . Similar results were obtained
Table 1 Distinguishing features between lichen sclerosus and lichen
Features Lichen sclerosusLichen planus
Often in women,
not in men
Nail dystrophyNo Occasionally
Itch Soreness, pain
Lichenoid papule Lichenoid papule
White reticulate striae
Histology Epidermal atrophy,
collagen in upper
dermis with dermal
Fig. 1 A 41-year-old woman with asymmetric vulvar lichen sclero-
sus limited to the upper part of the right labium minus and the
interlabial sulcus: depigmentation, hyperpigmentation, and sclerosis
leading to circumscribed retraction of the right labium minus
Fig. 2 An 80-year-old woman with extensive, long-standing, ano-
genital lichen sclerosus affecting the entire vulva, perineum, perianal
region, genitocrural folds, inner thighs, and buttocks: depigmentation,
hyperpigmentation, erythema, sclerosis, erosions, telangiectasias, and
complete loss of labia minora
by Simpkin and Oakley  in their clinical review of 202
affected women. Labia minora was affected in 87 % of
women, perineum in 85 %, clitoris in 72 %, and the peri-
anal region in 50 %. LS can koebnerize and may first arise
in an episiotomy scar. Extragenital lesions are seen more
frequently in women than men, and occurred in 11 % of the
327 female patients examined by Cooper et al. , in
13 % of the 357 female patients examined by Meyrick
Thomas et al. , and in 13 % of the women reviewed by
Simpkin and Oakley .
Vulvar LS often begins around the periclitoral hood with
a sharply demarcated, slightly elevated, nonspecific ery-
thema (Fig. 4), progressing to the labia minora, vestibule,
and perineal and perianal regions. Edema, particularly of
the periclitoral hood, may be prominent. Fragility is a
hallmark of LS, becoming manifest in erosions, fissuring,
purpura, and ecchymoses. Fissuring is especially common
between the clitoris and urethra, in the interlabial sulci, and
at the base of the posterior fourchette (Fig. 5). Tearing
during sexual intercourse or physical examination is com-
mon. The typical lesions are porcelain-white papules and
plaques with follicular delling and hyperkeratosis (Fig. 3).
The area evolves into a dry, hypopigmented, sclerotic, and
later atrophic lesion. The resulting crinkling or cellophane
paper-type appearance is pathognomonic. LS is a scarring
process and may cause complete loss of the labia minora,
sealing of the clitoral hood, and burying of the clitoris
Fig. 3 A 65-year-old woman with lichen sclerosus showing the
characteristic ‘figure-of-eight’ distribution: typical primary lesions are
the ivory-white, flat, polygonal papules, giving lichen sclerosus the
name ‘white-spot-disease’ in the past. Note the involvement of the
interlabial sulci, clitoris, and clitorial hood
Fig. 4 A 17-year-old woman with lichen sclerosus affecting primar-
ily the periclitorial region: the periclitorial hood is sealed and the
clitoris buried. Fissure in the upper part of the periclitorial hood and
diffuse erythema of the vestibule
Fig. 5 A 27-year-old woman with lichen sclerosus affecting the
vulva and perineum: perineal pallor, sclerosis, and sagittal fissure
32S. K. Fistarol, P. H. Itin
(Fig. 4). Smegmatic pseudocyst can result from adhesions
of the clitoral hood (Fig. 6) . Fusions of tissue may
occur across the midline, rarely leading to problems with
micturition. Severe introital narrowing interfering with
intercourse may rarely occur, but is seen more frequently in
the LS /LP overlap syndrome (Fig. 7) .
Vulvar melanosis can result from chronic disease.
Genital lentiginosis frequently presents with dark brown-
black macules with variegated pigmentation and irregular
borders. Genital nevi occasionally exhibit similar charac-
teristics particularly in the context of chronic inflammation
and LS. Histologic examination can easily differentiate
mucosal lentiginosis from melanoma, but melanocytic nevi
superimposed on a background of anogenital LS, both
clinically and histologically, may mimic malignant mela-
noma . Clark et al.  reported that more than one-
third of genital nevi sent to them in consultation (20/56)
had previously been misdiagnosed as melanoma. Histo-
logic interpretation is particularly difficult in the setting of
LS, when papillary dermal melanocytes entrapped in
sclerosis often display cytologic atypia and the lympho-
cytic infiltrates can disrupt dermal nests. Carlson et al. 
identified ten melanocytic lesions clinically suspected to be
malignant melanoma or atypical melanocytic nevi arising
in anogenital LS of the vulva and perineum. The suggestive
clinical symptoms or signs were irregular borders, black
clinical appearance, recent growth, and/or recent onset of
pruritus. Melanocytic proliferations arising in LS were
interpreted histologically as junctional melanocytic nevi
(five cases), compound melanocytic nevi (three cases),
intradermal melanocytic nevi (two cases), or malignant
melanoma (one case). Single cases of vulvar melanoma in
the setting of LS have been described, but are a rarity.
Vulvar pigmented lesions associated with LS are almost
always benign. Nevertheless, clinically suspicious pig-
mented lesions should be biopsied.
Itch is the main symptom, often worse at night and
sufficiently severe to disturb sleep. Chronic scratching
leads to subepithelial hemorrhage and superimposed lichen
simplex (Fig. 8). Pain, soreness, and dysuria may be a
consequence of erosions or fissures. A high proportion of
women of all ages reported that LS led to significant sexual
problems including dyspareunia and apareunia due to
continuing inflammatory disease as well as due to anatomic
changes and scarring from long-standing active disease
[44, 62]. Under treatment with clobetasol propionate oint-
ment, the Female Sexual Distress Scale score could be
reduced from 29 pretreatment to 15 post-treatment, and
with pimecrolimus cream from 27 pretreatment to 21 post-
treatment . Though adequate treatment will improve
sexual problems, women with LS continue to have signif-
icant sexual dysfunction. Disease severity does not always
correlate with severity of symptoms. LS may be entirely
asymptomatic and an incidental finding on examination.
Fig. 6 A 47-year-old woman with vulvar lichen sclerosus: diffuse
pallor, erythema, sclerosis, and telangiectasias, almost complete loss
of labia minora and smegmatic pseudocyst resulting from adhesions
of the clitorial hood
Fig. 7 A 75-year-old woman with lichen sclerosus/lichen planus
overlap syndrome: diffuse pallor, erythema, sclerosis, and telangiec-
tasias. Damage of the normal architecture with partial loss of labia
minora. Edema of the clitoris and the residual labia minora. Introital
erosions and narrowing of the introitus. Sagittal fissuring of the
perineum. Coincidental finding is an urethral caruncle
Vulvar dysesthesia may persist in spite of clinical control
of the disease.
5.1.2 Female Anogenital LS: Children
In 70 cases of LS in girls, the mean age at development of
symptoms was 5.0 years (range 1–12 years) and the mean
age at diagnosis was 6.7 years (range 3–14 years) . The
most common presenting symptoms were itching (72 %)
and soreness (61 %). Pain on defecation presenting as
constipation and bowel symptoms (24 %), dysuria (24 %),
and local bleeding (26 %) is seen significantly more fre-
quently in girls than in women . The skin may appear
bruised with purpura and ecchymoses (Fig. 9). In the
presence of hemorrhagic lesions, LS in girls can be mis-
taken for sexual abuse . However, the verification of a
diagnosis of LS does not exclude coincident sexual abuse,
since LS may be triggered by sexual abuse through the
Koebner phenomenon. Suspicion should be entertained
when LS arises in older prepubertal girls, if response to
treatment is poor, and in the case of associated sexually
transmitted infections .
Infantile perineal protrusion (IPP) occurs almost exclu-
sively in prepubertal girls and may be associated with LS in
a minority of patients . IPP appears as a pyramidal soft-
tissue protrusion with a tongue-like lip in the midline just
anterior to the anus. IPP with clinical and histologic fea-
tures of LS has been described. LS may appear concur-
rently with IPP or may develop subsequently.
LS may improve symptomatically but usually does not
entirely resolve at puberty. A retrospective study of 21
revealed that the disorder appeared less active in most
cases, but definite physical symptoms and signs persisted in
76 % . A prospective follow-up of 12 children with LS
showed that 25 % achieved complete remission prior to
menarche. Seventy-five percent of the girls had active LS
at puberty and required maintenance therapy after menar-
che. Fifty percent had significant disturbance of vulvar
5.1.3 Male Genital LS: Adults
Nelson and Peterson  found the highest prevalence of LS
in men at ages 61 years or older, but Edmonds et al. 
found an adult peak late in the fourth decade. They identified
retrospectively a total of 329 patients with a clinical diag-
nosis of male genital LS from a dermatology-centered
multidisciplinary setting. Only 6 % of the affected men were
circumcised at presentation. LS is a disease of the uncir-
cumcised man. In 70 % of men LS involved the prepuce, in
60 % the glans, and in 40 % both the glans and prepuce were
affected. Seventeen percent had meatal/urethral involve-
ment. Urethral involvement usually starts at the meatus and
postinflammatory scarring may lead to meatal and urethral
stenosis and obstruction, complications that frequently
necessitate surgical management. Only 1.5 % had extra-
genital involvement and none had perianal involvement. In a
review of 522 male patients with LS, Depasquale et al. 
found that the disease was limited to the prepuce and glans
in 57 % of patients, meatal involvement occurred in 4 %,
and urethral involvement in 20 %.
Fig. 8 An 81-year-old woman with lichen sclerosus with superim-
posed lichen simplex: marked lichenification and excoriations,
ecchymoses, telangiectasias, erosions, and ulceration on a hypopig-
mented and erythematous background. Fissuring of the right genito-
crural fold. Complete loss of normal vulvar architecture
Fig. 9 A 6-year-old girl with anogenital lichen sclerosus: slight
sclerosis of the clitorial hood and the inner aspect of labia majora.
Prominent contusiform hemorrhage
34 S. K. Fistarol, P. H. Itin
Early manifestations are greyish or bluish-white discol-
orations of the glans and/or the inner surface of the prepuce
(Fig. 10), sometimes with considerable telangiectasia. Itch
may be present. Subsequently, skin thins, sclerotic plaques
appear, and the prepuce becomes tightened and nonretrac-
tile. Phimosis with the risk of paraphimosis develops
(Fig. 11). One report documents that 14 % of primary
(congenital) phimosis occurring in young adults and 40 % of
secondary (acquired) phimosis in older patients were due to
progressive LS . The involved inelastic skin is prone to
fissuring during sexual activity. Purpura, bullae, erosions,
and ulcerations may be encountered (Figs. 12, 13). Fifty-five
percent of affected men report sexual symptoms as painful
erections and erectile dysfunction . Eighteen percent
report urologic symptoms such as dysuria, narrowing of the
urinary stream, and poor urinary flow. Twenty-nine percent
are asymptomatic .
5.1.4 Male Genital LS: Children
Boys most commonly present in need of circumcision
because of associated phimosis . The reported inci-
dence of LS in boys undergoing circumcision for phimosis
ranges from 10 to 40 % [67–69]. A prospective study of
1,178 boys presenting with phimosis found that 40 % had
LS on circumcision pathology, with the highest incidence
in boys aged 9–11 years (76 %) . Perianal involvement,
as in adult men, is extremely rare.
5.1.5 Extragenital LS
The most common locations for extragenital disease are the
buttocks, thighs, breasts, submammary area, neck, back
and chest, shoulders, axillae, and wrists. Extragenital LS
Fig. 10 A 37-year-old man with genital lichen sclerosus: grayish-
bluish, white discoloration of the glans and inner surface of the
prepuce, sclerosis of the frenulum, and freckled melanosis
Fig. 11 A 65-year-old man with genital lichen sclerosus: depigmen-
tation, macular erythema, and severe sclerosis leading to phimosis
Fig. 12 A 57-year-old man with genital lichen sclerosus: depigmen-
tation, atrophy of the glans with crinkling appearance, ecchymoses,
and macular melanosis
Fig. 13 A 73-year-old man with genital lichen sclerosis: severe
sclerosis, scarring of the coronal sulcus, and large ulceration of the
lesions are prone to koebnerization and may express
themselves in areas of physical trauma, continuous pres-
sure, and scarring. Lesions begin as polygonal, bluish-
white, slightly elevated papules (Fig. 14). Papules coalesce
into plaques, which with time become increasingly atrophic
and get a wrinkled surface (Fig. 15). Telangiectasias and
follicular plugging may become prominent (Fig. 16). The
fragility of the flattened epidermal-dermal interface may
give rise to bullous and hemorrhagic lesions. Extragenital
LS is much less symptomatic than genital LS, underlining
the role of occlusion and maceration in the etiology of
pruritus, soreness, and pain in genital LS.
In the early stages of LS not only the symptoms and clinical
signs, but also the histologic picture may be uncharacteristic
. The histologic features in early LS are quite subtle and
may overlap with those seen in psoriasis or LP, with luminal
hyperkeratosis and hypergranulosis of the adnexal structures,
mild irregular, occasionally psoriasiform acanthosis, and
focal basement membrane thickening. Early dermal changes
are subepithelial edema, homogenized collagen, and dilated
blood vessels immediately under the basement membrane.
epidermal lymphocyte exocytosis and lymphocytic/lympho-
[70, 71]. The classic histologic features of more advanced
elastic fibers, and hyalinization of the lamina propria with an
underlying lymphocytic infiltrate, but prominent acanthosis
may be a feature particularly in vulvar LS. In a study of 121
cases of vulvar LS, changes in lichen simplex chronicus or
spongiotic dermatitis, dermal eosinophils, and a frequent
LS cases presenting with eosinophilic spongiosis, marked
lymphocyte exocytosis, dermal eosinophils, and excoriations
showeda poorsymptomatic responseto treatment.The cause
might be a superimposed allergic contact dermatitis. Patch
testing is recommended for these individuals.
The pathology for LS is far from being always conclu-
sive. Thus, for the final diagnosis, the clinicopathologic
correlation is pivotal .
The various treatment options for anogenital LS are sum-
marized in Table 2.
Fig. 14 A 65-year-old woman (same patient as in Fig. 3) with genital
and extragenital lichen sclerosus on the volar aspects of the wrists:
characteristic bluish-white, polygonal, slightly elevated papules
coalescing into plaques
Fig. 15 An 81-year-old woman with genital and extragenital lichen
sclerosus on the upper thighs: papular, partially atrophic lesion with
wrinkled surface, telangiectases, and hemorrhage
Fig. 16 A 65-year-old woman with extragenital LS on the volar
aspect of the wrist (same patient as in Fig. 3 and Fig. 14) with
prominent follicular plugging
36S. K. Fistarol, P. H. Itin
In a prospective open-label trial, 34 women were treated
with topical corticosteroid cream once daily for 1 month.
Seventy-one percent became symptom free and 29 %
experienced a partial response. Maintenance therapy con-
sisted of an emollient alone. Seventy percent of the women
could maintain initial treatment response after a median
follow-up of 58 months with cold cream alone . After
induction of remission with topical corticosteroids in
women with vulvar LS, Cattaneo et al.  also observed a
good symptomatic control of the disease with a mainte-
nance therapy with an emollient cream alone during the
follow-up of 24 weeks.
6.2 Topical Corticosteroids
Most patients with LS will respond to topical corticosteroids
with relief of symptoms and clinical and histologic
improvement. When patients with LS do not respond to
topical corticosteroids of an adequate potency and a suffi-
cient duration, diagnosis should be doubted and reappraised,
and contact allergy to a constituent of the cream, secondary
infections, or malignant evolution should be excluded.
For lack of sufficient long-term studies there are still
concerns about the long-term safety of topical corticoste-
roids. Feared adverse effects of long-term, topical corti-
formation, rebound reactions, fungal infections, reactiva-
tion of human papilloma virus (HPV) and herpes simplex
virus infection, or systemic absorption.
6.2.1 Female Anogenital LS
Since the first published small study showing the effec-
tiveness of ultrapotent topical corticosteroids in the treat-
ment of adult vulvar LS , several authors have
confirmed these positive results [53, 55, 75–78]. Topical
ultrapotent corticosteroids gave improvement of symptoms
in nearly all patients, complete relief of symptoms in about
70 %, and complete remission of skin changes in one-fifth
of women with anogenital LS [54, 55]. Thirteen women
with vulvar LS treated with clobetasol propionate 0.05 %
cream twice daily for 12 weeks showed a significant
reduction in epidermal atrophy, hyperkeratosis, epidermal
basal cell liquefaction, inflammatory infiltrate, and hya-
linization of dermal collagen after treatment. In four of the
biopsies, no specific features of LS remained after
12 weeks of treatment . There are no randomized
controlled trials providing evidence on how often, how
long, and in which potency the corticosteroids are to be
applied. However, the recent British Association of Der-
matologists guidelines advocate their use and propose a
detailed regimen . They recommend for a newly diag-
nosed case to apply clobetasol propionate 0.05 % ointment
once daily at night for 4 weeks, then on alternate nights for
4 weeks, and then twice weekly for a further 4 weeks. If
symptoms should recur with reduced frequency the patient
should use the treatment more often until symptoms
resolve. An ointment formulation is usually better tolerated
than a cream base.
Long-term follow-up in 83 women (with a median fol-
low-up time of 4.7 years) confirmed a high rate of relapses
of 84 % at 4 years , but even with long-term, ultra-
potent, topical corticosteroid maintenance treatment, tol-
erance in this cohort was excellent. Surprisingly, no
atrophic effects were observed.
Several studies showed that less potent topical corti-
costeroids such as mometasone furoate or triamcinolone
are also effective to treat vulvar LS [80, 81]. Cattaneo
et al.  treated 31 women with biopsy-proven vulvar
LS with a regimen of 0.1 % mometasone furoate cream
application once daily for 4 weeks and then twice weekly
for 8 weeks. After 12 weeks of treatment, all women had
a significant improvement in the gross aspects of the
disease and a very dramatic decrease in symptoms, with
nearly all the subjects having complete symptomatic
remission. No adverse effects were observed. The use of
a less potent topical corticosteroid could be safer in
particular for the long-term maintenance treatment of LS.
In order to minimize corticosteroid exposure, it is the
successful practice of many clinics to lower the potency
and frequency of applied corticosteroids once remis-
sion has occurred and maintenance therapy is required
In the treatment of childhood vulvar LS, an excellent
response to a potent topical corticosteroid (betamethasone
dipropionate 0.05 %) without serious adverse events was
first described in a small case series in 1997 . Other
authors confirmed the results in prepubertal girls treated
Table 2 Treatment of anogenital lichen sclerosus
Minimize irritants, soap substitution, avoidance of urinary contact
Moisturization with emollients
Treatment of infections
Ultrapotent or potent topical corticosteroid once daily at night for
4 weeks, then on alternate nights for 4 weeks, and then twice
weekly for a further 4 weeks. Continued suppressive therapy
according to the ongoing inflammatory activity
In corticosteroid-resistant cases, consider circumcision in men,
application of topical calcineurin inhibitors, topical retinoids in
hyperkeratotic lesions, systemic retinoids, or photodynamic
Surgery for intraepithelial neoplasia or carcinoma
with ultrapotent topical corticosteroids likewise without
having significant adverse effects [7, 84, 85]. Cooper et al.
 performed a larger study including 74 girls with vulvar
LS treated with potent or superpotent topical corticoste-
roids. Seventy-two percent became symptom free and 25 %
experienced subjective improvement, 22 % showed com-
plete resolution of clinical signs, and 67 % showed partial
resolution of clinical signs. A long-term follow-up of
childhood LS in 15 girls with a mean follow-up of
4.7 years showed the best therapeutic response with an
early aggressive treatment, a high recurrence rate of 60 %
after 1 year from the first clearing, and the need for
maintenance therapy .
6.2.2 Male Genital LS
Clobetasol dipropionate 0.05 % cream applied for
2–16 weeks improved itching, burning, pain, dyspareunia,
phimosis, and dysuria and reduced all histologic features in
22 men with penile LS. Twenty-seven percent required
additional circumcision . Also, in another series the
majority of 66 men responded to ultrapotent topical corti-
costeroids as first-line therapy. Twelve percent required
circumcision . In the most recent case series, treatment
with topical clobetasol propionate was successful in 59 %
of 185 men. Forty-one percent failed topical corticosteroid
treatment and were subsequently circumcised .
In boys with genital LS, topical medium-potency corti-
costeroids resulted in improvement in clinically and his-
tologically early and intermediate stages of LS, but were
ineffective in late stages with established scarring [89, 90].
There are several studies concerning the efficacy of topical
corticosteroids in the treatment of phimosis [91–94]. As we
know, about 40 % of phimoses in boys are proven histo-
logically to be LS . In an open-label trial including 54
boys with phimosis, clobetasol propionate cream was an
effective treatment in 70 % . A prospective, random-
ized, double-blind, placebo-controlled study in 30 boys
with phimosis confirmed a high efficiency of topical clo-
betasol propionate ointment . Yang et al.  showed
in a prospective randomized study with 70 boys with phi-
mosis that both moderately potent topical corticosteroids
and ultrapotent topical corticosteroids are equally effective
in treating phimosis with a response rate of 77 % and 81 %,
respectively. In 462 boys with phimosis, of whom 12 had
LS, the overall response rate after 6 weeks of topical cor-
ticosteroids was 86 % . In the subgroup with LS the
response rate was 67 %. The treatment success was
maintained after a median follow-up of 22 months. This
study shows that topical corticosteroids are an effective
treatment in boys not only for LS, but also for phimosis of
6.2.3 Extragenital LS
Although regularly used in this setting, there are no pub-
lished randomized controlled trials or case series reporting
the use of topical corticosteroids for extragenital LS.
6.3 Topical Calcineurin Inhibitors
The topical calcineurin inhibitors (TCIs) pimecrolimus and
tacrolimus have a significant anti-inflammatory activity,
immunomodulatory effects, and a low systemic immuno-
suppressive potential. Several reports advocate the use of
TCIs in the treatment of anogenital LS as safe and effective
and emphasize the lack of atrophogenicity as an advantage
over topical corticosteroids. However, atrophy in LS as an
adverse effect of treatment with topical corticosteroids has,
so far, not clearly been documented. The question of
atrophogenicity is difficult to answer as atrophy is part of
the LS process itself.
Other authors have vehement objections to applying
TCIs in a disease with an intrinsic malignant potential and
fear that TCIs in LS will increase the risk of malignant
progression [31, 95]. The US FDA collated worldwide
reports and found 19 malignancy-related adverse events
related to topical tacrolimus and 10 cases related to topical
pimecrolimus . Three of these were observed in
genital LS treated with TCIs, one penile SCC in a 57-year-
old man with genital LS treated with tacrolimus, one vulvar
SCC in a 75-year-old woman with genital LS treated with
tacrolimus, and one low-grade SCC in a 71-year-old
woman treated with pimecrolimus. In 2007, Fischer and
Bradford  reported on a 73-year-old woman with a
10-year history of hypertrophic LS and genital psoriasis
who presented with intractable superimposed inflammatory
vulvitis. She was treated with topical pimecrolimus 1 %
cream on the assumption that she was either allergic to or
intolerant of topical corticosteroids. One month after
commencing therapy, she suddenly developed a rapidly
growing vulvar tumor. This was excised and proved to be a
well differentiated SCC. In the UK, advice has been issued
that topical tacrolimus and pimecrolimus should not be
applied to malignant or to potentially malignant skin
lesions and that treatment should be short term .
Finally, it should be kept in mind that TCIs are con-
siderably more expensive than topical corticosteroids. This
is particularly significant in a disease with a usually chronic
The role of TCIs in the treatment of inflammatory
mucosal disorders , and in particular of LS, has been
recently reviewed . The use of TCIs in LS is off label.
The patient has to be informed about this circumstance
prior to the prescription.
38S. K. Fistarol, P. H. Itin
In 2004, the first case reports of LS treated with a twice-
daily application of pimecrolimus cream 1 % in children
[100, 101] and adults  were published, each with
considerable improvement of clinical signs and symptoms
within 6 weeks of treatment and almost complete remis-
sion within 12–16 weeks of treatment.
A pilot study in 2007 evaluated the efficacy and safety
of pimecrolimus cream 1 % applied twice daily for up to
6 months for severe vulvar LS . Complete remission
with relief from itchiness, pain, and inflammation was
achieved in 35 % (9/26) after 2 months and in 42 % (11/26)
after 6 months. After 2 months of treatment, a 3.5-fold
increase in type I and a 7.5-fold increase in type III col-
lagen synthesis of the affected areas could be observed.
There were no systemic adverse reactions. Mild local
burning and itching during the first 3–14 days were
reported by 50 % of the women. Three patients had with-
drawn from the study during the first week because of
pruritus and/or no satisfactory response. Blood concentra-
tions of pimecrolimus checked in 10/26 patients were
undetectable in all cases.
At the same time another prospective study evaluating
the efficacy, tolerability, and safety of pimecrolimus cream
1 % in 16 postmenopausal women with histologically
proven vulvar LS was published . After 3 months of
treatment, complete remission was achieved in 69 % and
partial remission in 25 % of the patients and biopsies in
eight patients showed that typical histologic features of LS
had disappeared. The only adverse effect was a mild to
moderate burning sensation at the application site during
the first week of treatment in one-third of women.
The effects of pimecrolimus on p53, Bcl-2, and Ki-67
with active LS . After 2 months of treatment with
twice-daily pimecrolimus cream 1 %, complete remission
was achieved in 76 % and partial remission in 4 %. Post-
treatment biopsies revealed decreased p53 staining and an
increased number and staining intensity of Bcl-2-positive
basal keratinocytes. Whether the decrease in p53 and
increase in Bcl-2 expression will provide protection from
malignant progression warrants long-term follow-up. The
clinical remission correlated with a marked reduction in
lymphocytes of the vulvar skin, mainly CD3-negative
T lymphocytes and CD8-negative cytotoxic T lymphocytes.
Moreover, the number of CD57-negative natural killer cells
was decreased. Pimecrolimus did not affect B cells .
The first and only comparative study is a double-blind,
randomized controlled trial comparing the safety and effi-
cacy of clobetasol with pimecrolimus in the treatment of
vulvar LS . Seventeen women in the pimecrolimus
group and 19 women in the clobetasol group all had
biopsy-proven vulvar LS. Pimecrolimus cream was applied
twice daily and clobetasol cream once daily for 12 weeks.
At the end of the treatment period, clobetasol was found to
be superior to pimecrolimus in improving histologically
controlled inflammation. However, this fact was not clini-
cally relevant since there was no statistically significant
difference in subjective improvement of pruritus, burning,
and pain or objective clinical assessment by the investi-
gator between the two treatment groups.
Kim et al.  recently added an oral case of LS in a
7-year-old girl successfully treated with pimecrolimus
cream 1 % twice daily for 8 weeks. After unsatisfactory
treatment with ultrapotent topical corticosteroids, the
lesion improved within 4 weeks of treatment with pime-
crolimus and disappeared after 12 weeks.
The first case reports of LS treated with tacrolimus oint-
ment 0.1 % in three women, in three prepubertal girls,
and in two men have been published in 2003 and 2005
[109–112]. Complete remission was achieved in all patients
after 6 weeks to 10 months of treatment.
In the first pilot study, 16 women with histologically
proven vulvar LS were treated with tacrolimus ointment
0.1 % twice daily . By the end of 3 months, 12.5 %
achieved a complete response, and this was maintained at
12 months. Fifty percent experienced partial improvement
and wished to continue on tacrolimus. 37.5 % were non-
responders. There was no influence of age, menopausal
status, or duration of symptoms on treatment response. One-
third reported a transient, mild, local burning sensation.
A second pilot study reported 11 women with vulvar LS
achieving complete remission in 36 % and partial remis-
sion in 55 % after 3 months of treatment with tacrolimus
ointment 0.1 % .
A multicenter, phase II trial evaluated the safety and
efficacy of tacrolimus ointment 0.1 % for the treatment of
LS . Eighty-four patients (49 women, 32 men, and 3
girls) aged between 5 and 85 years with long-standing,
active LS (79 with anogenital and 5 with extragenital
localization) were treated with tacrolimus ointment 0.1 %
twice daily for 16 weeks. If deemed clinically beneficial,
treatment was continued until week 24. Complete remis-
sion was achieved in 43 % and partial remission in 34 % of
patients. Maximal effects occurred between weeks 10 and
24 of therapy. Transient burning and itching during the first
days of treatment were the most common adverse events,
leading two patients to intermittently stop tacrolimus
application and one patient to withdraw from the study.
Infections such as genital herpes and vulvovaginal candi-
diasis each occurred in 2 % of patients. No malignancy was
observed during an 18-month follow-up period.
Lichen Sclerosus 39
Sotiriou et al.  treated ten postmenopausal women
with recalcitrant vulvar LS with tacrolimus ointment 0.1 %
twice daily for 8 weeks. Mild local burning during the first
days of treatment occurred in four patients. Reduction in
pruritus, burning, and pain occurred within the first
2 weeks of treatment in all patients. Mean values in the
visual analog scale decreased from 2.55 at baseline to 0.95
at week 8. Analysis of objective scores, however, showed
only a minor influence on hyperkeratosis, atrophy, sclero-
sis, and depigmentation, probably explained by the short
duration of treatment of only 8 weeks.
Matsumoto et al.  reported on a 5-year-old girl with
vulvar LS unresponsive to mild topical corticosteroids. She
was treated successfully with tacrolimus ointment 0.03 %
once daily with complete remission after 14 weeks without
any adverse effects.
6.4 Topical Testosterone
The treatment of LS with topical testosterone has been
abandoned because of ineffectiveness [74, 118, 119], due
to the superiority of ultrapotent topical corticosteroids
[120, 121], systemic absorption, and virilizing effects in
female patients [122–125].
6.5 Topical and Systemic Retinoids
Although topical and systemic retinoids have been shown
to be useful, they did not become widely accepted in the
treatment of vulvar LS, probably due to their well known
adverse effects and severe teratogenicity and the need for
long-term treatment in a usually chronically relapsing
Several case series showed definitely respectable results
in the treatment of vulvar LS with systemic and topical
retinoids [126–128]. Topical 0.025 % tretinoin once a day,
5 days per week, for 1 year improved symptoms, clinical
appearance, and histopathologic features in 22 women
treated for vulval LS . Cutaneous irritation was mild
Six of eight women treated with oral etretinate with an
initial dose of 1 mg/kg/day for vulval LS showed improve-
ment in symptoms and clinical signs, and in four of five
women improvement was reflected also in histopathology
. Romppanen et al.  also observed excellent
with vulvar LS treated previously unsuccessfully with top-
ical estrogen and corticosteroids. In over 90 % of women,
symptoms, signs, and histopathologic features improved
significantly. Finally, the good results from treatment with
oral retinoids in women with severe vulvar LS have
been confirmed in a double-blind, placebo-controlled study
.Acitretin20–30 mg/dayfor16 weeksledtotreatment
response in two-thirds of women. All patients treated with
systemic retinoids experienced the typical retinoid adverse
effects in various degrees.
Only one published study deals with retinoids as a
treatment in male genital LS . It is a randomized,
double-blind, placebo-controlled study in which 52 male
patients with severe, long-standing LS resistant to topical
treatment with ultrapotent corticosteroids, were random-
ized to receive acitretin 35 mg/day or placebo for 20
consecutive weeks. Complete response was achieved by
36.4 % of the acitretin group versus 6.3 % of the controls,
while 36.4 % versus 12.5 % achieved partial resolution,
respectively. Mean time to partial response was 17 weeks
and to complete response 20 weeks. The well known,
expected adverse effects of retinoids were observed in a
high percentage of patients.
In women with anogenital LS, surgery should be limited to
patients with associated vulvar intraepithelial neoplasia or
malignancy or to correct scarring interfering with normal
function . Introital stenosis may lead to difficulties with
micturition or sexual intercourse and may require introital
widening. Surgery should not be performed until the dis-
ease activity has ceased.
In penile LS, surgery has a more important role. In male
patients who have failed medical management or who
present with advanced disease with structural changes due
to scarring, circumcision is indicated and has a success rate
of 76–100 % [33, 64, 131]. Removal of the foreskin alters
the local environment, which plays an important role in the
etiogenesis of penile LS. LS may koebnerize in the cir-
cumcision scar. Meatal stenosis can be treated with ventral
meatotomy or dorsal V-meatoplasty . In cases of ure-
thral stenosis, urethroplasty with buccal and/or bladder
mucosa grafts may be necessary .
6.7 Phototherapy and Photodynamic Therapy
6.7.1 Psoralen plus UVA (PUVA) Cream
Photochemotherapy for Genital LS
Reichrath et al.  tretated five women with vulvar LS
with topical psoralen plus UVA (PUVA) therapy using
8-methoxypsoralen (8-MOP)-containing cream. The mean
number of treatments administered was 25.6 (range 5–104),
and the mean cumulative UVA dose was 44.2 J/cm2(range
4.0–180). Two patients showed marked improvement with
complete reduction in pruritus and an increase in tender-
ness, two showed improvement, and one had stable disease.
40 S. K. Fistarol, P. H. Itin
6.7.2 Bath and Peroral PUVA Photochemotherapy
for Extragenital LS
In 1997, the first case of extragenital LS successfully
treated with PUVA bath photochemotherapy over a period
of 6 weeks was described . The cumulative UVA
dose was 31.7 J/cm2. The single UVA dose ranged from
0.3 to 2.3 J/cm2. After 24 treatments, the skin lesions were
almost completely cleared and pruritus was diminished.
A 10-year-old girl with LS on the trunk was treated with
systemicPUVA with peroral
(0.75 mg/kg) and a total UVA dose of 61 J/cm2.
After 3 months of oral PUVA there were no new lesions
and previous ones resolved completely or with residual
Another woman with extensive extragenital LS showed
great clinical and subjective improvement with 0.1 % ta-
crolimus ointment and PUVA (single dose of 1–4.6 J/cm2
and total cumulative dose of 79 J/cm2) .
Seven women with severe genital LS uncontrolled by ul-
trapotent topical corticosteroids were treated with UVA1
. They received 15–65 UVA1 exposures to the peri-
neum. The maximum single dose varied from 20 to 140 J/
cm2, the total dose from 190 to 2200 J/cm2. Two women
with coexistent extragenital LS also received whole-body
UVA1 treatment. Three achieved moderate and two
achieved minimal improvement of the genital LS. Two of
these five responders relapsed. Response of extragenital
lesions tended to be greater than that of genital lesions.
In an open-label study, Kreuter et al.  presented the
improvement of extragenital LS in ten patients treated by
UVA1 phototherapy (four sessions per week for 10 weeks,
20 J/cm2low-dose UVA1 per session, 800 J/cm2cumula-
tive dose). An obvious softening of sclerotic plaques was
observed after the tenth session in most patients, whereas
repigmentation of former porcelain-like polygonal patches
was detected after the 20th irradiation in all patients.
Increased corium thickness was decreased to the normal
range and there was also a highly significant increase of
dermal density after UVA1 irradiation.
An individual case of extragenital LS treated successfully
with narrow-band UVB has been reported .
6.7.5 Photodynamic Therapy
Photodynamic therapy (PDT) seems to be a reasonably
effective alternative therapeutic modality to treat LS
resistant to conventional treatment, as shown by several
case series [139–142]. The first results were published in
1999  and are consistent with the results obtained by
the subsequent studies [140–142]. Twelve women with
genital LS underwent one to three cycles of 5-ALA PDT
(5-aminolevulinic acid and argon dye laser). Ten of the
twelve women experienced good symptomatic control of
their disease after treatment, with alleviation of pruritus
and pain sustained for 6 months . Altogether, the
studies showed no substantial influence on the objective
clinical and histopathologic scores. Common adverse
effects were pain and a stinging and burning sensation
during treatment. Local erythema occurred up to 1 week
after therapy. The most recent study included 100 women
with genital LS treated with PDT . Partial or even full
remission of subjective symptoms and objective clinical
signs could be observed. After six courses of PDT the
immunohistochemical staining in vulvar LS showed
increasing microvessel density and decreasing lymphocytic
infiltration [143, 144].
In a descriptive cohort study with a mean follow-up of
66 months, 327 patients (74 girls and 253 women) with
vulvar LS have been treated with topical corticosteroids
. Clinical signs improved in nearly all patients, but only
22 % of the girls and 23 % of the women showed complete
resolution of clinical signs with return to normal skin
texture and color . The concept that prepubertal LS
resolves at puberty appears not to be true in the majority of
patients. Seventy-five percent of girls who develop LS
prior to puberty will continue to require maintenance
therapy after menarche [52, 53].
There is a significant risk for women with vulvar LS to
develop scarring with loss of vulvar architecture and nor-
mal function. Cooper et al.  showed in their study of
327 women that a delay in diagnosis of 2 years or less was
associated with less scarring at diagnosis. In a second long-
term study (mean follow-up 6.2 years), the authors com-
pared the data of 84 fully compliant women with 45 partly
compliant women with vulvar LS . Ninety-eight per-
cent of the fully compliant patients achieved complete
symptom control, including ability to resume sexual
activity without pain. None had disease progression. In
partially compliant patients, only 75 % achieved complete
symptom control and 35 % experienced progression of
disease with scarring and fusion.
A survey of men with genital LS with a mean length of
follow-up of 15.2 months showed that 59 % of 185 men
treated medically with topical clobetasol propionate toge-
ther with adjunctive measures, such as strict avoidance of
contact with soap and urine, and moisturization, became
symptom free . If maximal conventional medical
management had failed, with persistent dyspareunia or
rash, penile carcinoma in situ, and urologic dysfunction,
then circumcision was recommended. In 76 % of those
cases circumcision was curative; 24 % of the total cir-
cumcised cases required on-going medical therapy despite
A rare complication of genital LS is SCC (Fig. 17). In
the literature the incidence of SCC in vulvar LS is reported
to be between 0.3 and 4.9 % [1, 10, 55, 145, 146]. In vulvar
LS, advanced age and clinical evidence of squamous
hyperplasia are independent risk factors for developing
vulvar carcinoma as shown in a retrospective case-control
study by Jones et al.  If histologic changes of LS
adjacent to vulvar SCCs are searched, LS has been found in
33 % of 1287 patients with vulvar SCC (range 7–85 %)
. Chiesa-Vottero et al.  examined 44 thin (B5-
mm tumor thickness), invasive vulvar SCCs. LS was
present in 32 %. In patients with adjacent LS, all SCCs
were of the keratinizing type. In the warty- and basaloid-
type SCC, LS was not present. In the study by Cooper et al.
, 6 of 327 women with vulvar LS developed SCCs. The
delay in diagnosis of vulvar LS was greater in the six
women with SCC than in those women with no malignancy
(15.3 vs. 4.4 years). However, because of the small num-
bers of SCCs this difference was not statistically signifi-
cant. In the long-term follow-up study by Bradford and
Fischer , 5 of 45 partly compliant women developed
SCC, whereas none of the 84 fully compliant women
In a review of 86 biopsies of male genital LS, six penile
SCCs (7 %), one erythroplasia of Queyrat, and one
verrucous carcinoma were found, corresponding to a
malignancy rate of 9.3 % (8/86) [149, 150]. The average
lag time from onset of LS to the emergence of malignancy
was 18 years (range 10–34 years). In five of those eight
patients HPV 16 was detected . Barbagli et al. 
reexamined the histology of 130 men with genital LS.
Eleven (8.5 %) showed premalignant or malignant histo-
pathologic features, including seven SCCs, two verrucous
carcinomas, one erythroplasia of Queyrat, and one SCC
associated with verrucous carcinoma. Retrospective anal-
yses of patients with penile carcinoma show LS in a high
number of cases. In 2001, Powell et al.  reviewed 20
penile SCCs and found histologic features and/or a clinical
history of genital LS in 11 (55 %). Perceau et al. 
reviewed 18 cases of penile SCCs and found a histology of
LS in eight of them (44 %). All eight SCCs associated with
LS were negative for oncogenic HPV types. Velazquez and
Cubilla  examined 207 penectomy and circumcision
specimens with SCCs and giant condylomas and among
them histologically identified 68 cases of LS (33 %).
It is not assured if medical treatment of LS can prevent
the evolution to malignancy. However, the existing long-
term follow-up studies suggest that early diagnosis and
early treatment with good compliance might not only lower
rates of malignancies but also prevent scarring [54, 81].
The etiology of LS is still unknown. There is evidence
supporting an autoimmune etiology in genetically predis-
posed patients. Patients with LS and their relatives have
more frequently occurring, autoimmune-related disorders
and autoimmune antibodies than controls. Thyroid disease,
alopecia areata, vitiligo, and pernicious anemia should be
considered in a patient diagnosed with LS. The detection of
autoantibodies to ECM1 and to BMZ components suggests
that autoimmunity to these components might contribute to
the pathogenesis of LS. However, those antibodies rather
then being causative and involved in the initiation, might
be a result of damage to the BMZ, and contribute to the
progression of the disease. An infectious etiology has been
proposed, but could never be definitively confirmed. The
role of B. burgdorferi is still unclear. Hormonal influences
do not seem to play a major role.
LS may lead to scarring and destruction of the normal
genital architecture. In a high proportion of affected
women and men, LS causes sexual dysfunction.
The diagnosis of LS is usually clinical. In clinically
unclear cases, a histologic examination is required.
Although classic histologic findings will confirm the
diagnosis, a nonspecific histology does not rule out LS. The
clinicopathologic correlation is pivotal. Patients under
Fig. 17 An 89-year-old woman with long-standing anogenital lichen
sclerosus. She developed a nodular lesion firm to palpation on the left
side of the vulva. Biopsy confirmed an invasive carcinoma
42 S. K. Fistarol, P. H. Itin
follow-up will need a biopsy in the case of a persistent area
of hyperkeratosis, erosion or erythema, or a warty or
nodular lesion, in the case of any area resistant to adequate
treatment, in the case of unclear pigmentation, and if a
second-line therapy is going to be introduced.
Topical corticosteroids are highly effective, and remain
the first-line treatment for LS. They often give relief of
symptoms in the first few days of treatment. Emollients are
recommended as a supportive treatment. TCIs are an
alternative treatment option for patients who have failed
therapy with ultrapotent corticosteroids, or who have a
contraindication for the use of corticosteroids. However,
there are still serious concerns for an increased risk of
malignant transformation of genital LS due to local
immunosuppression by long-term use of TCIs in a disease
with an intrinsic potential for malignant evolution [31, 95].
With TCIs, prolonged therapy of up to 24 weeks may be
necessary to obtain optimal response.
Systemic retinoids have been used in the past with
considerable success in severe vulvar LS, but in women of
childbearing age the teratogenic risk limits their use.
Surgery should be limited to patients with associated
malignancy or to patients who need correction of func-
tionally restricting, scarring processes.
Phototherapy and PDT are possible third-line therapies
in cases resistant to the aforementioned treatments.
Genital LS is associated with scarring and an increased
risk for vulvar and penile SCC. Long-term follow-up and
ongoing suppressive treatment are mandatory.
this article. The authors have no conflicts of interest that are directly
relevant to the content of this article.
No sources of funding were received to prepare
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in
any medium, provided the original author(s) and the source are
This article is distributed under the terms of the
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