Female genital diseases
Lichen sclerosus of vulva
Salient features
|
· Inflammatory
condition of the vulva occurring at any age. · Most
symptomatic in childhood and postmenopausal years (low estrogen levels). · Cellophane
paper-like texture to the white plaques classically. · Chronic,
long-term disease leads to scarring and resorption. · Chronic
active disease increases risk of vulvar squamous cell carcinoma. · Treatment
is with superpotent steroid (clobetasol
propionate) ointment. · Maintenance
therapy is needed for long-term control. |
Introduction
Lichen
sclerosus is a common inflammatory dermatosis with a predilection for ano‐genital skin. It is primarily a disease of the
superficial dermis or submucosa that leads to ivory-white scar-like atrophy. The etiology is still unknown but LS is a genetically
determined autoimmune disorder, and antibodies to extracellular matrix protein
1 have been identified in about 75% of women with the disease.
Epidemiology
Age
Lichen sclerosus is the commonest cause of chronic vulvar
dermatosis. The prevalence is 1:300–1:1,000. The onset is bimodal in
prepubertal girls between 8 and 13 years of age and perimenopausal women.
Sex
Lichen
sclerosus is 10 times more common in females than males.
Associated
diseases
It
is associated with other autoimmune disorders in 21% of patients, with thyroid
disease being the commonest association.
Pathogenesis
As in
most inflammatory diseases, genetic predisposition contributes to the
development of lichen sclerosus, as it may be found in monozygotic and
fraternal twins. In addition, association with the MHC class II antigen HLA-DQ7
is observed in a relatively large study. The existence of a relevant
susceptibility gene for sclerosis within this region of the MHC is underlined
by the finding that the same region is associated with a greater risk of
organ-specific autoimmune diseases. Even though inflammation seems essential
for initiation and progression of lichen sclerosus, the mechanisms leading to
subsequent sclerosis remain speculative.
Perhaps
with the exception of autoantibodies against extracellular matrix protein 1
(ECM-1), no specific immunologic parameters have been identified in patients’
sera that clearly correlate with either risk of disease or disease activity.
IgG autoantibodies against ECM-1 are found in 80% of patients with lichen
sclerosus. Moreover, in female patients with lichen sclerosus, there is a
higher prevalence of autoimmune diseases (especially autoimmune thyroid
disease) and ANA than in male patients with lichen sclerosus.
Oxidative
stress may also play a role in the pathogenesis of lichen sclerosus, based upon
analysis of lesional skin that showed lipid peroxidation of epidermal basal
cell layers, oxidative DNA damage, and oxidative protein damage.
Pathophysiology
It
is possible that chronic occluded contact of urine with susceptible epithelium
is involved in the pathogenesis of ano‐genital lichen sclerosus. The barrier function of wet skin is
diminished and it is more permeable to irritants. In addition, wet skin has an
increased frictional coefficient and higher microbial content. Perianal lichen sclerosus
occurs in 30% of women with genital lichen sclerosus and its occurrence has
been associated with urinary incontinence. This pattern reflects the areas of
ano‐genital
skin that come into contact with urine. Men rarely if ever have perianal lichen
sclerosus, probably because the male perineum is rarely exposed to urine.
Pathology
The classic histology is a thinned
epidermis with flattening of the rete pegs and vacuolar degeneration of the basal
layer. Vacuolar degeneration of the
basal layer and flattening of the rete ridges predispose to the development of
blisters, which may become hemorrhagic. The
underlying papillary dermis is hyalinized and sclerotic. Below the hyalinized
area is a band‐like zone of lymphohistiocytic infiltrate. Squamous hyperplasia may be present and may be associated with an
increased risk of SCC. Loss
of elastic fibers in the upper dermis is typical for
lichen sclerosus and is not observed in morphea. Subepidermal
clefting, telangiectasias and hemorrhage within the hyalinized papillary dermis is frequently observed. Early
on, the papillary dermis may be edematous and homogenous, but, with time,
hyalinization and sclerosis are observed.
Genetics
A
positive family history is recognized in 12% of patients.
Predisposing
factors
Local
friction or rubbing may induce lesions of lichen sclerosus via the Koebner
phenomenon, and some cases of early-onset lichen sclerosus may be associated
with the antiandrogenic oral contraceptive pill.
Clinical
features
The presenting
symptom is usually itching, which is often severe. Because
vulvar skin affected by lichen sclerosus is fragile, scratching often produces
painful erosions. Many women, by the time they come for treatment, exhibit late
signs of lichen sclerosus, including remarkable textural changes and scarring
with loss of normal vulvar architecture. Scarring and narrowing of the
introitus may make intercourse painful, even intolerable. Constipation is a common feature in
girls with prepubertal disease.
Lichen
sclerosus begins with ivory colored papules or plaques that often occur first
on the anterior vulva and periclitorally. Although these papules and plaques
are sometimes smooth and somewhat waxy, especially when they occur on moist
skin, the classic presentation is one of a well-demarcated plaque with a whitened and sclerotic epithelium and a shiny, flat atrophic crinkled cellophane-like surface, which may become confluent, extending around the vulval and
perianal skin in a figure‐of‐eight configuration. Dilated pilosebaceous or sweat duct orifices
filled with keratin plugs (dells); if plugging is marked, surface appears
hyperkeratotic. Generally, the skin is quite thin and fragile, with erosions
and purpura, telangiectases, bullae (sometimes hemorrhagic),
being common manifestations. Some women, particularly those who experience
intolerable itchiness, exhibit thickened hyperkeratotic skin with extensive
secondary changes, including fissuring, crusting, and even bleeding. Vestibular involvement is rare and vaginal lesions do not
occur, as LS seems to spare non-cornified stratified squmous epithelia (mucosal
epithelium). Perianal lesions occur in approximately 30% of female patients, in
contrast with men who do not develop perianal lesion.
Extragenital lichen sclerosus of keratinized skin occurs
in in 10% of women with
vulvar lichen sclerosus and is most often located on the upper trunk and arms.
Usually, extragenital lesions are asymptomatic. The classic lesions seen on the extragenital skin are ivory
white papules and plaques with follicular delling.
LS are a scarring dermatosis and
therefore architectural change is common. Burying of the clitoris secondary to midline
fusion or fusion of the labia minora to the labia majora may occur. In untreated or severe disease, there may be total loss
of labia minora and significant introital
narrowing resulting from anterior and posterior labial fusion, sometimes
resulting in a tiny opening into the vestibule. Sexual intercourse may become
impossible.
Complications
and co‐morbidities
Sexual dysfunction results from scarring and introital
narrowing. Four to five percent of patients are reported to develop vulval squamous cell
carcinoma in the natural course of lichen sclerosus. Squamous cell carcinomas
occurred primarily in patients with chronic hyperkeratosis or erosions. The histological patterns associated
with SCC arising on LS include epithelial hyperplasia and differentiated
intraepithelial neoplasia (dysplastic changes that are confined to the basal
layers).
With effective topical therapy, this risk is understood to be lower.
Disease
course and prognosis
There
is generally a good response to a super‐potent
topical steroid but some patients have a relapse of symptoms requiring repeated
treatment. There is still uncertainty whether LS in prepubertal girls remits
spontaneously at puberty.
Pitfalls in the diagnosis of lichen
sclerosus
· Wrong/incomplete
diagnosis in the case of squamous cell carcinoma.
· Lichen
sclerosus, especially when bullous, hemorrhagic, or erosive, may be confused
with child abuse.
· Inappropriate
surveillance for steroid adverse effects.
· Irritant
dermatitis caused by over washing of the anogenital area may imitate lichen
sclerosus and facillitate the occurrence of contact dermatitis.
Diagnosis
Fully developed
lichen sclerosus with hypo pigmentation and distinctive shiny or crinkled
textural changes is easily recognized.
A
biopsy can confirm the diagnosis and is essential in atypical disease or if
there is a failure to respond to treatment.
Treatment
The main aim of therapy is to bring the disease under control as
quickly as possible with the fewest side effects. Although topical
glucocorticoids reduce symptoms, they do not always normalize the skin texture
or prevent scarring. The super‐potent topical corticosteroid, clobetasol propionate 0.05%,
is first line treatment. The regimen currently recommended for a newly diagnosed
case is initially clobetasol propionate ointment once nightly for 4 weeks, then
alternate nights for 4 weeks, and twice a week for a further month. A 30 g tube
of clobetasol propionate should last 12 weeks, and the patient is then
reviewed. This alleviates symptoms in the majority of patients, often within
weeks. As
an adjunct therapy for the first week or two to control scratching and hasten
healing, sedating dosages of an antihistamine or a tricyclic antidepressant are
helpful. The clobetasol propionate is then
used as and when required to control itching. Some patients go into complete
remission and do not require further treatment. Others will continue to have
flares and remissions and they are advised to use clobetasol propionate
ointment as required. Any
infection must be controlled. A soap
substitute is also recommended such as emulsifying ointment.
No
other treatments for lichen sclerosus produce the striking and prompt benefit
of a topical superpotent glucocorticoid. Both safety
and efficacy of clobetasol in the treatment of genital lichen sclerosus are
documented for all age groups and in both sexes. Intralesional triamcinolone is used in resistant
areas. Recent reports have suggested the
use of the calcineurin inhibitors tacrolimus or pimecrolimus as steroid‐sparing alternatives. The use of these topical
immunosuppressants should be limited to the treatment of the rare cases of LS
that prove unresponsive to a potent topical steroid. The treatment should be a
short course and it should not be used long term as the safety of these
immunosuppressants is still unknown, particularly as the condition carries a
risk of neoplastic change. Ciclosporin and UVA1 have also been used to treat
recalcitrant disease.
Surgical
therapies, including cryotherapy, vulvectomy, carbon dioxide laser
vaporization, pulsed dye laser therapy, and photodynamic therapy is only indicated for the management of functional problems
caused by post inflammatory scarring, premalignant and malignant lesions.
Lichen planus of vulva/vagina
Salient features
· Four
distinct forms of genital lichen planus are observed: (1) papules or plaques in
the setting of generalized cutaneous lichen planus; (2) erosive disease; (3)
hypertrophic disease; and (4) lichen planopilaris
· Although
cutaneous disease is often self-limiting, mucous membrane disease is more
persistent
· The
classic findings in cutaneous disease are violaceous, flat-topped papules and plaques;
lacy white streaks typically occur on the genitalia as well as the oral mucosa
· Erosive
lichen planus often involves multiple mucous membrane sites – in particular,
the vulva, vagina, and oral mucosa
Introduction
Lichen
planus (LP) is an idiopathic inflammatory dermatosis that can affect the skin
and mucous membranes. It may affect the ano‐genital
skin and mucosa without involvement elsewhere.
Epidemiology
Incidence
and prevalence
Vulvovaginal lichen planus is much less
common than vulvar lichen sclerosus with a likely prevalence of 1 in
2,500–4,500. It is often misdiagnosed as lichen sclerosus. Approximately 50% of
women with cutaneous lichen planus have genital involvement.
Age
The
symptoms usually start in the fifth and sixth decades of life.
Associated
diseases
There
is an association of LP with autoimmune diseases including alopecia areata,
vitiligo and thyroid disease.
Pathophysiology
Lichen planus
probably a T cell-mediated inflammatory
disorder causing
damage to epidermal cells that express altered self or foreign antigens on
their surface, but the exact etiology is unknown. Infectious
triggers, particularly hepatitis C viral infection, may be associated with
mucosal lichen planus. There is
an association of erosive lichen planus of the vulva with autoimmune disease.
Pathology
On a cornified epithelium there is
hyperkeratosis, irregular acanthosis with a typical saw‐tooth appearance of the rete pegs, an increased granular
layer, and liquefactive degeneration of the basal layer with a closely apposed, dermal band‐like lymphocytic infiltrate. The acanthosis and
hyperkeratosis are marked in the hypertrophic form. Eosinophilic colloid bodies
may be seen.
Because
there is loss of the epithelium in erosive disease, the specimen should include
the edge of the erosion as well as the surrounding lacy reticulated skin.
Despite this, it is sometimes difficult to unequivocally confirm the disease,
but histologic evaluation can aid in excluding other disorders in the
differential diagnosis.
Clinical
features
History
The
symptoms will depend on the clinical type of LP. Itching may be predominant in
the classic and hypertrophic variants, whereas soreness, pain and dyspareunia
are the common complaints in erosive LP. If vaginal disease is present, a sero‐sanguinous discharge and postcoital bleeding may occur.
Presentation
The
clinical features vary with clinical type.
Clinical variants
There are four distinct
presentations of genital lichen planus
but sometimes there may be overlapping features.
1.
Classic/papular
lichen planus
In classic lichen
planus, the genital lesions are similar to those in other cutaneous sites but
lacy reticulation (wickham striae) may be very
prominent. The typical violaceous papules are
seen on the mons
pubis, outer labia majora and minora, interlabial sulci and clitoral hood. These may coalesce into
small plaques or annular lesions. Hyperpigmentation is common. Scarring is not a
feature of classic lichen planus. The lesions are usually self-limiting.
2.
Hypertrophic
lichen planus
This is the least common form of LP seen on the genital
skin. Thickened, intensely pruritic hyperkeratotic white
plaques, sometimes with a violaceous edge, are seen on the labia majora,
perineum and perianal skin.
Vaginal lesions do not occur in classic or hypertrophic LP.
3.
Lichen
planopilaris
Follicular
keratotic papules are limited to the hair-bearing labia majora and the mons
pubis, but may also be seen on the scalp and trunk and in the axillae.
4.
Erosive
lichen planus
Erosive LP is the commonest type to affect the female
genital area. On the vulva, symmetrical erosions are most commonly seen around
the vaginal orifice, edged by lacy white reticulations; similar lesions may
also occur on the labia. Vaginal involvement can
present with a discharge, with velvety red
erosions or bright red, glazed erythema of the vaginal mucosa, which is friable and bleeds when touched. Vaginal synechiae
and adhesions develop, which may rapidly lead to vaginal stenosis. Oral
involvement is frequently observed, usually in the form of a desquamative
gingivitis, but lacy white reticulations and erosions may also occur. Erosions
limited to the perianal area alone have been described.
Lichen planus,
especially when erosive, produces remarkable scarring. Resorption of the labia
minora and obliteration of the clitoris under an agglutinated clitoral hood are
very common. Narrowing of the introitus occurs more often and more severely
than with lichen sclerosus, and vaginal adhesions can close the vagina,
preventing both intercourse and introduction of a speculum.
Differential diagnosis
The
principal differential diagnosis is:
· lichen
sclerosus
· autoimmune
bullous disease, including mucous membrane pemphigoid
· plasma
cell vulvitis
· Behçet
disease
· vulvar
intraepithelial neoplasia or SCC
Direct
immunofluorescence may be necessary to exclude an autoimmune bullous disease.
Orogenital ulceration raises the possibility of Behçet disease. Early lichen
planus may be confused with vulvar eczema and there may be superimposed lichen
simplex chronicus. For hypertrophic disease, vulvar intraepithelial neoplasia,
SCC, and lichen simplex chronicus are the major entities in the differential
diagnosis.
Complications
The
inflammation, pain, and scarring commonly cause sexual dysfunction, and at
times, anger and depression. Vulvar squamous cell carcinoma has been well
described in patients with erosive genital lichen planus. Long-term evaluation
of these patients is advised because of the risk of malignant transformation;
the incidence of the latter has been estimated to be ~2.4%.
Disease
course and prognosis
Classic
LP often clears completely with no scarring. Hyperpigmentation may take months
to resolve. Erosive and hypertrophic disease tends to run a chronic course with
flares of disease.
Investigations
The diagnosis of lichen planus is made either
by biopsy or by the identification of classic lacy lesions in association with
other typical mucous membrane lesions.
Treatment
|
THERAPIES FOR ANOGENITAL
LICHEN PLANUS |
|
First-line |
|
· Soap
substitutes and emollients · Super
potent topical corticosteroids for vulva · For
vaginal disease, corticosteroid foams*, enemas*, suppositories* or
ointments (± dilators) |
|
Second-line |
|
· Longer-term
maintenance with super potent topical corticosteroids or combined moderately
potent corticosteroid/antifungal/antibacterial preparations · Surgery
to correct narrowing of introitus and reverse clitoral burying in women · Topical
calcineurin inhibitors · Intralesional
corticosteroid (hypertrophic disease) · Systemic
corticosteroids · Systemic
immunosuppressants · Systemic
antibiotics (minocycline ± nicotinamide) |
The aggressive treatment of vaginal lichen planus is
crucial for patient comfort. Meticulous local care with early treatment of
infection, minimization of external irritants, and attention to any underlying
atrophy of estrogen deficiency are important measures. A vaginal dilator should
be used daily to prevent adhesions of the vaginal walls. Emotional support and
careful patient education regarding the nature of the disease, its prognosis,
and its therapy are vital.
Pruritic,
noneroded vulvar lichen planus is usually quite well managed simply by the
application of a potent topical glucocorticoid ointment. Hypertrophic disease may require intralesional
corticosteroids.
The
management of erosive lichen planus is more difficult, as the disease is often
more persistent. The majority of patients will respond to a 3-month course of
topical clobetasol propionate 0.05% ointment applied to the vulva (as described
for lichen
sclerosus) and thereafter can be maintained on moderately potent
corticosteroids. A combination of a moderately potent corticosteroid with a
topical antifungal cream may be as effective as more potent corticosteroids,
particularly for maintenance therapy. For mild-to-moderate disease, a gram of
the glucocorticoid ointment can be inserted into the vagina as well, or hydrocortisone acetate 25 mg
rectal suppositories can be inserted nightly into the vagina
For severe disease, systemic steroids are used and the
least toxic is deep intramuscular triamcinolone 1
mg/kg up to 80 mg/dose. This may be repeated monthly for 3 months and limited
to four doses per year. Patients are warned about adrenal suppression and given
fluconazole 150
mg weekly to prevent candidiasis. Any patient with vulvar disease receiving an
intravaginal glucocorticoid should be told of her increased risk for yeast
infection. There is little tendency for erosive vulvovaginal lichen planus to
remit, but it can be well controlled. The severity tends to wax and wane,
sometimes as a result of secondary infections, exposure to irritants, or stress
but more often for no identifiable cause. Bursts of oral prednisolone or
intramuscular triamcinolone can be helpful for flares.
Topical tacrolimus and
pimecrolimus
have been reported to be useful in the treatment of vulvar lichen planus, but
these medications are irritating. They can be used as “steroid sparers” once
the inflammation is controlled.
For refractory disease, systemic immunosuppressants (e.g.
mycophenolate mofetil) and oral hydroxychloroquine are used. Low-dose weekly
methotrexate, as for oral erosive lichen planus, may be helpful for severe
disease.
Surgery to release vulval and vaginal
adhesions may be required, but the use of super‐potent
topical steroids in the early postoperative phase is vital to prevent re‐stenosis.
Psoriasis of vulva
Introduction
Psoriasis
may affect the ano‐genital area as part of generalized disease but can occur in
isolation. Psoriasis of the anogenital region may appear quite different from
psoriasis at other sites. The typical silvery scale is lost, as in other
flexural sites such as the axillae and submammary region.
Pathology
Flexural
psoriasis does not always have the typical histological features of psoriasis
seen elsewhere and there may be marked spongiosis and papillary edema.
Environmental
factors
Friction
and occlusion are important aggravating factors in vulval psoriasis.
Clinical
features
Most
patients complain of itching but soreness, pain and dyspareunia can occur,
particularly if the lesions become fissured.
Although vulvar psoriasis generally is
accompanied by psoriasis in other typical locations, the vulva is a common site
of Koebnerization. Vulvar psoriasis usually affects only fully keratinized
hair-bearing skin, sparing the modified mucous membrane of the inner labia
majora and the labia minora. Well‐demarcated dusky red smooth plaques
are seen on the outer labia majora, and extension on to the mons pubis,
inguinal folds, perianal skin and gluteal cleft is common. Rather than thick,
silvery scale, the moistness of inverse psoriasis, a glazed, shiny surface
texture is seen. Persistent, painful fissuring of the
perianal area and the intergluteal cleft can be a severe problem.
Disease
course and prognosis
Ano‐genital psoriasis generally runs a chronic course.
Investigations
Psoriasis
is usually diagnosed clinically and a biopsy is rarely needed.
Treatment
Genital psoriasis often responds well to topical therapy.
A mid- or high-potency glucocorticoid ointment generally is required for
significant clinical or symptomatic improvement. Calcipotriene
ointment, tacrolimus
ointment, or pimecrolimus
cream can be tried as well, but some patients find these too irritating. For widespread disease, methotrexate, cyclosporine, or
TNF inhibitors are required.
Therapeutic ladder
First line
·
Emollients and moderately potent
topical steroid once daily on a reducing regimen
Second line
·
Calcineurin inhibitors
·
Calcipotriol (but with care because
of irritancy)
Third line
·
Systemic agents and biologics may be
used if severe, but these are rarely necessary for isolated genital disease.
Vulvar Dermatitis
Salient features
·
Appearance ranges from mild erythema to
marked lichenification
·
Pruritus and soreness are the main complaints
·
A mixed etiology is common
·
Exogenous irritants and allergens must be
sought
Introduction
Although anogenital
dermatitis has traditionally been subdivided into endogenous dermatitis (e.g.
seborrheic dermatitis, atopic dermatitis), lichen simplex chronicus, and
exogenous dermatitis (e.g. allergic or irritant contact dermatitis), in
practice it is often difficult to distinguish between subtypes. A mixed
picture, in which endogenous dermatitis is worsened by exogenous irritants or
allergens, is common. Lichen simplex chronicus may develop secondarily to other
anogenital diseases such as candidiasis, psoriasis, and lichen sclerosus.
Pathogenesis
The
majority of patients with vulvar dermatitis have an endogenous predisposition,
having either an atopic background or seborrheic dermatitis. The anogenital
area is susceptible to irritants, and allergic contact dermatitis is very
prevalent in this site; the latter is usually due to topical medications or
personal hygiene products (e.g. “wet wipes” that contain
methylisothiazolinone). Psychological issues and local environmental problems
such as heat, sweating, and over-cleansing may be contributing factors.
Clinical features
The
cutaneous features are varied, ranging from mild, usually poorly demarcated
erythema to severe lichenification. Symptoms include pruritus, pain, and
dyspareunia in women. In lichen simplex chronicus, scratching and rubbing is associated
with unremitting pruritus. Fissuring is common, especially perianally. The
typical anogenital sites affected are the labia majora and the mons pubis in
women, the crura and scrotum in men, and the perianal area in both sexes.
Lichenification is most often seen on the scrotum in men and the labia majora
in women. Signs of seborrheic dermatitis (e.g. a scaly scalp, greasy scaling
and erythema of nasolabial folds and eyebrows), as well as erythema at other
flexural sites such as the inframammary crease, intergluteal fold and axilla,
should be sought. Atopic dermatitis at other sites will usually be obvious from
the history and examination.
Histologic evaluation may be required to confirm the
clinical diagnosis (e.g. lichen sclerosus) or to exclude more unusual
etiologies (e.g. extramammary Paget disease).
Differential diagnosis
The
diagnosis is usually made on the basis of clinical appearance, but a skin
biopsy can be helpful in excluding other diagnoses. For example, plaques of
psoriasis are well-circumscribed than those of dermatitis. Extramammary Paget
disease should also be considered, but these lesions are also sharply
demarcated and usually asymmetric. It is important to identify irritants and
possible allergens through a careful history and possibly patch testing. In
addition, bacterial and Candida cultures
should be performed to exclude superimposed infection, which is common in the
anogenital region. Early lesions of lichen sclerosus may be indistinguishable
from dermatitis.
Treatment
The
regular use of bland emollients and the substitution of an emollient for soap are
recommended. Exacerbating factors, including stress, heat, excessive washing, and
use of premoistened personal hygiene wipes (“wet wipes”) and candidiasis,
should be identified. A major therapeutic aim is reduction of pruritus and
soreness. If the area is acutely inflamed, potent topical
corticosteroids, often in combination with topical antifungal agents, topical
antibacterial agents and/or topical immunomodulators, are helpful. Over a
period of a few weeks, the topical corticosteroid can be tapered to one that is
less potent. When lichenification is present, it is especially important to
break the itch–scratch cycle. Additional therapies include sedative
antihistamines or tricyclic antidepressants, usually doxepin, at bedtime.
