Lichen planus
Salient features
·
Idiopathic inflammatory disease of the skin, hair, nails and
mucous membranes, seen most commonly in middle-aged adults
·
Flat-topped violaceous papules and plaques favoring the wrists,
forearms, genitalia, distal lower extremities, and presacral area
·
Clinical variants include actinic, annular, atrophic, bullous,
hypertrophic, inverse, linear, ulcerative, vulvovaginal–gingival, lichen
planopilaris, lichen planuspigmentosus, and drug-induced
·
Some lichenoid drug eruptions have a photo distribution, while
others are clinically and histologically indistinguishable from idiopathic
lichen planus
·
The most commonly incriminated drugs include
angiotensin-converting enzyme (ACE) inhibitors, thiazide diuretics,
antimalarials, quinidine, and gold
·
Histologically, there is a dense, band-like lymphocytic
infiltrate and keratinocyte apoptosis with destruction of the epidermal basal
cell layer
·
In this T-cell-mediated autoimmune disorder, basal keratinocytes
express altered self-antigens on their surface
Definition
Lichenoid disorders are inflammatory
dermatoses characterized clinically by flat‐topped,
papular lesions and histologically by lichenoid tissue reaction, characterized by
vacuolar alteration of epidermal basal cells intimately associated with a
band-like infiltrate of primarily lymphocytes in the papillary dermis. Lichen planus is the prototype of lichenoid dermatoses.
Lichenoid tissue
reaction (LTR)
During the initiation
of LTR, pDCs are activated by circulating immune complexes, viruses or by self-DNA/LL37 complexes induced during
skin injury, leading to the abundant production of IFN-α. The IFN-α signal may
represent an early event in the initiation of lichenoid skin reaction. IFN-α
induces the production of CXCR3 ligands in structural cells of the skin and
activates cytotoxic T cells secreting TH1
cytokines either directly or indirectly through activation of mDCs. Activated
cytotoxic TH1 cells and pDCs amplify perpetuate the production of
CXCR3 ligands through secretion of IFNs leading to additional recruitment of
pDC and pathogenic T cells, and development of a LTR phenotype.
Introduction
Lichen planus is a common disorder of stratified squamous
epithelia in which auto-cytoxic T lymphocytes trigger apoptosis of epithelial cells
leading to chronic inflammation.
Lichen planus (LP) is an idiopathic inflammatory disease
of the skin, hair, nails and mucous membranes, often with a chronic course with relapses and periods of
remission. Classic LP is characterized by pruritic, violaceous
papules that favor the extremities. Histologically, a dense, band-like
lymphocytic infiltrate is seen underlying an acanthotic epidermis with
hypergranulosis, apoptosis, and destruction of the basal cell layer. It has a
multifactorial etiology with complex interactions of innate and adaptive immune
responses and the disorder has been associated with multiple environmental
exposures, including viral infections, medications, vaccinations and dental
restorative materials. LP is an autoimmune reaction against epitopes on
lesional keratinocytes that have been modified by viral or drug antigens.
Epidemiology
Cutaneous LP affects 1% of the adult population, whereas
oral lesions affects up to 4% of the population. The onset of LP occurs most commonly between
the ages of 30 and 60 years, women are affected approximately twice as often as
men.
Pathogenesis
LP represents
T-cell-mediated autoimmune damage to basal keratinocytes that express altered
self-antigens on their surface, which can be
triggered by a variety of exogenous antigens, including drugs, metals (gold or
mercury) or infection (hepatitis C virus). A critical component
for the generation of effector T cells with cytotoxic potential is due to
presentation of these exogenous antigens in the context of antigen-presenting
cells.
Genetics
There could be
HLA-associated genetic susceptibility that would explain a predisposition in
certain persons. Familial cases are reported. LP occurs in up to
10% of first-degree relatives of affected patients. Cases of familial LP tend to
have an earlier age of onset (affecting children and young adults), a higher
relapse rate, and more frequent oral mucosal involvement. Different HLA
haplotypes are reported in familial lichen planus, including HLA-B7, -Aw19,
-B18, and -Cw8. In nonfamilial lichen planus, HLA-A3, -A5, -A28, -B8, -B16, and
-Bw35 are more common. HLA-B8 is more common in patients with oral lichen
planus as a sole manifestation, and HLA-Bw35 is more strongly associated with
cutaneous lichen planus.
Environmental
factors
Environmental
factors including viral infections, drugs, and contact allergens have been
potentially associated with LP.
Viruses
Of the many potential exogenous antigens, greater
attention has been focused on the possible role of viruses, particularly
hepatitis C virus (HCV). Of the various types of LP, it is the oral form that
is most commonly viewed as a manifestation of HCV infection. The PCR technique
detected HCV RNA in 93% of oral LP lesions, suggesting HCV replication within
LP lesions.
Other viruses have been implicated
in the pathogenesis of LP, including hepatitis B virus (HBV), human herpes
virus 6 (HHV‐6) and HHV‐7 and varicella zoster virus.
Typically, hepatitis B vaccines have been shown in some patients to trigger LP,
often after the second injection of vaccine.
Contact allergens
Contact allergy to a variety of metals within
dental restorations causes exacerbation or induction of oral LP, positive patch
test results, and then regression or complete clearing after removal of the
sensitizing metal and replacement with other materials. Because involved
allergens are dissolved and spread via saliva, mucosal reactions may extend
beyond the contact areas. The metals that aggravate oral LP include amalgam
(mercury), copper and gold. Although approximately
95% of patients had improvement after removal of the sensitizing metal, 75% of
patients with negative patch test results also reported clearing of oral LP
after removal of the metal and replacement with other materials. One possible
explanation for this finding is that mercury served as an irritant and induced
lesions via the Koebner phenomenon.
Of note, the development
of contact allergy to metals within dental restorations in patients with LP
could be explained by easy penetration of the metal via damaged mucosa.
Drugs
Cutaneous eruptions identical to LP (both clinically and
histologically) have been linked to a variety of drugs. The terms “lichen
planus-like” and “lichenoid” are often used to describe this phenomenon. A wide
variety of drugs have been associated with lichenoid drug eruptions. The
mechanism by which certain drugs can induce a lichenoid tissue reaction in
susceptible hosts is unknown, but appears to be similar to LP. The most
commonly incriminated drugs include angiotensin-converting enzyme (ACE)
inhibitors, thiazide diuretics, antimalarials, quinidine and gold.
Betel nut
Social use of the betel nut is relatively common in India
and South‐East Asia. The product that is chewed, betel quid, is a
mixture of substances, including the areca nut and betel leaf, and is
associated with oral LP.
Lichen planus‐like contact dermatitis
An LP‐like eruption occurs in up to 25% of persons exposed to
chemicals found in color developer such as para‐phenylenediamine.
Immunopathology
Phases of
lichen planus
A. In the induction phase, keratinocytes and plasmacytoid
dendritic cells (pDCs), upon stimulation of their Toll-like receptors (TLRs) by
pathogens or endogenous ligands, can release type 1 IFNs (e.g. IFN-α); this
represents an early event in the cascade leading to T-cell-mediated epidermal
damage. Activated keratinocytes, via production of IL-1β and TNF-α, can induce
activation and migration of DCs. Chemokines, such as IP-10/CXCL10, released
locally by pDCs, serve to attract CXCR3-expressing CD8+ or CD4+ effector memory
T cells (which have differentiated from naive T cells within lymph nodes
following presentation by DCs of self-peptides modified by exogenous antigens
[viruses, medications and contact allergens]). Additional chemokine and
chemokine receptor pairs have also been implicated in this process and the
precise mix of chemokines and cytokines released into the tissue plays an
important role in determining the composition of the inflammatory infiltrates.
B. In the evolution phase, effector T cells (Te) that come to express skin
homing receptors (E-selectin ligands) migrate into the inflammatory site and
upon recognition of antigens, are activated and release proinflammatory
cytokines and cytotoxic granules, which in turn cause epidermal injury. In addition,
Fas/FasL interactions can trigger cell death of both lymphocytes and
keratinocytes with possible elimination of potentially harmful auto aggressive
T cells. “Inflammatory” and “homeostatic” chemokines produced by keratinocytes
direct the traffic of not only “pathogenic” T cells (Te) but also ‘immune
surveillance” T cells (Ts) or regulatory T cells (Treg) into the sites; the
relative balance of chemokines produced may determine the outcome of the T-cell
mediate immune response.
Clinical features
The seven Ps—(1) purple, (2) polygonal, (3) planar, (4)
pruritic, (5) papule, (6) plaque and (7) persistent describe LP. The primary
lesion is a firm, 1 to
3-mm flat-topped papule with
irregular
angulated border (polygonal-shaped).
WICKHAM 1895 described the characteristic appearance of whitish striae and
punctuations that develop atop the flat surfaced papules. The surface is
slightly shiny or transparent and close inspection of the
surface shows a lacy, reticular pattern of crisscrossed, thin white lines
(Wickham’s striae), seen best with hand lens after application of a drop of
mineral oil. The latter
correspond histologically to focal thickening of the granular layer. Wickham striae are readily apparent by dermoscopy. Newly
evolving lesions are pink-white, but over time they assume a distinctive
violaceous or purple hue with a peculiar waxy luster. Lesions that persist for
months may become thicker and dark red (hypertrophic lichen planus). Papules can be isolated or they may cluster
or coalesce into larger plaques, or annular or diffusely papular
(guttate), or linear, appearing in response to a scratch or trauma (Koebner
phenomenon). Rarely, a line of papules may extend the length of the extremity.
Vesicles or bullae may appear on preexisting lesions or on normal skin. Typically, a greyish brown
pigmentation can be observed in lesions that have resolved due to deposition of
melanin in the superficial dermis. Annular lesions are especially common on the
penis and rarely may be the predominant type of lesion present, later leading
to atrophy. A variant in which groups of ‘spiny’ lesions resembling keratosis
pilaris develop around hair follicles called lichen planopilaris. Co‐localization of LP and vitiligo has
been reported. LP can affect any part of the body surface, but the most
frequently involved sites are the flexor surfaces of the wrists and forearms,
the dorsal surface of the hands, anterior aspect of the lower legs, neck, and
the lumbar region and around the ankles. The ankles and shins are the commonest
sites for hypertrophic lesions. When the palms and soles are affected, the
lesions tend to be firm and rough (hyperkeratosis) with a yellowish hue. Isolated
lesions of LP have been reported to involve one or both eyelids or the lips.
Pruritus is a
fairly consistent feature in LP; occasionally, pruritus is completely absent.
Hypertrophic lesions usually itch severely. Paradoxically, there is seldom evidence
of scratching, as the patient tends to rub to gain relief. Itching at sites
without visible skin lesions can occur. In the mouth, the patient may complain
of discomfort, stinging or pain; ulcerated lesions are especially painful.
Great discomfort may be caused by hot foods and drinks.
Natural history and
morphology of lichen planus
Acute eruptive lichen planus usually begins as
erythematous papules which progress and turn violaceous. Few of these lesions
may further coalesce to form plaques that may be violaceous or even
hypertrophic hyper pigmented type. Lesions resolve with classic post
inflammatory hyper pigmentation.
Clinical variants
Many variations in the clinical presentation have been
described and are generally categorized according to (1) the configuration of
lesions, (2) the morphologic appearance, or (3) the site of involvement. These
variations are patterned by subtle or unknown properties of the disease. The
prototypic papule can be altered or modified in configuration, morphology, or
anatomic distribution.
|
The
most common sites of involvement in LP based on subtypes. |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Configuration of Lesions
Lichen planus, annular
Annular
lesions occur in approximately 10% of patients with LP and are usually scattered among
more typical lesions, but the former may represent the predominant finding. Annular
lesions commonly develop as arcuate groupings of individual papules that
develop rings or peripheral extension of clustered papules with central
clearing. The annular edge is slightly raised
and typically purple to white in color, while the central portion is depressed,
slightly atrophic, hyper pigmented or skin-colored. The most common site of involvement is the axilla, followed
by the penis, extremities, and groin. Most
patients are asymptomatic, while some have pruritus. Actinic lichen planus
seen on sun-exposed, dark-skinned young adults and children is frequently
annular in shape.
Linear Lichen Planus
Although
linear lesions frequently occur in sites of scratching or trauma in patients
with LP as a result of the Koebner phenomenon, the term linear LP is usually
reserved for lesions that appear spontaneously within the lines of Blaschko.
Morphology of Lesions
Lichen planus, hypertrophic
Hypertrophic
lichen planus (lichen planus verrucosus) usually occurs on the extremities,
especially the shins, dorsal aspect of the foot or around the ankles, and interphalangeal joints. Additionally,
they tend to be highly pruritic, refractory to treatment, and associated with
relapse. After a long time, papules lose their characteristic features and
become confluent as reddish brown or purplish, thickened, elevated,
round-to-elongated (band like) plaques and nodules with a rough or
hyperkeratotic surface and may be covered by a fine adherent scale.
Occasionally, verrucous plaques develop. The lesions are usually symmetric and
tend to be chronic because of repetitive scratching. Chronic venous stasis
frequently contributes to the development of this condition. When such lesions eventually clear, an area of pigmentation
and scarring and some degree of atrophy may remain. Squamous cell
carcinoma may develop within a background of longstanding hypertrophic LP.
Atrophic Lichen Planus
Atrophic LP may represent a resolving phase of LP, given
the history of the lesions: papules coalesce to form larger plaques that over
time become atrophic centrally, with residual hyper pigmentation. They are most
common on the proximal lower extremities. Other reported sites included the
axillae, glans penis, and trunk. The clinical appearance of atrophic LP is
likely a result of marked thinning of the epidermis rather than degeneration of
elastic fibers, and the epidermal atrophy may be accentuated by the use of
potent topical corticosteroids. The lesions often resemble lichen sclerosus et atrophicus.
However, the histologic features are diagnostic.
Lichen Planus Pigmentosus
This
is a pigmentary disorder seen in India or in the Middle East, which may or may
not be associated with typical LP papules and favors
young to middle-aged adults with skin photo types III–V. It presents as
irregularly shaped or oval, slate grey to brownish black macules and patches in either sun-exposed areas (especially
the forehead, temples, neck and upper limbs)
or intertriginous zones, especially
the axillae, although it can be more widespread.
It is usually asymptomatic, but some patients describe mild pruritus or
burning. While the distribution is symmetric in the vast majority of patients, a
unilateral linear variant following the lines of Blaschko has also been described. It is mostly diffuse, but reticular, blotchy
and perifollicular forms are seen. The
palms, soles, nails and oral mucosa are usually not involved. LPP is a chronic
disorder with exacerbations and remissions. Histologic findings include an atrophic
epidermis, a vacuolar alteration of the basal cell layer with a scarce
lymphohistiocytic lichenoid infiltrate in
the upper dermis, and dermal melanophages.
The etiology of LPP is unknown. The photo distribution in
some patients suggests that UV can play a pathogenic role, and topical
application of mustard oil (which contains allylisothiocyanate, a potential
photosensitizer) and amla oil have been proposed as possible inciting agents.
In one uncontrolled study, lightening of the pigmentation occurred in 54% of
patients treated with topical tacrolimus for 12–16 weeks.
Lichen planus, actinic
Most patients are children or young adults. The onset of
this variant is during the spring and summer, and the lesions primarily involve
sun-exposed skin of the face, followed by the nape of the neck, the dorsal
surfaces of the hands and arms. The lesions usually consist of red–brown
plaques with an annular configuration with a thread, rolled edge or appear as discoid
patches, which have a deeply hyper pigmented center surrounded by a striking
hypo pigmented zone. Sunlight exposure appears to be central to the
pathogenesis of actinic LP. Melasma-like
hyper pigmented patches have been observed in actinic LP.
Lichen planus, guttate
Lesions are widely scattered and
remain discrete, may be all small (1 mm across) or larger (up to 1 cm), and
individual lesions seldom become chronic. Guttate psoriasis must be excluded.
Follicular Lichen Planus/lichen planopilaris
In lichen planopilaris, involvement of the hair follicle
is observed, both clinically and histologically. This variant is also called
follicular LP.
Follicular lichen
planus may occur alone or in association with other forms of cutaneous or
mucosal lichen planus. Individual keratotic follicular papules and studded
plaques are seen. Sites of predilection include the trunk and medial aspects of
the proximal extremities. Follicular lichen planus may affect the scalp is
likely to lead to a scarring alopecia.
Site of Involvement
Lichen Planus of the Scalp
Lichen planopilaris (LPP) or follicular lichen planus may
affect the scalp in a distinctive clinical and histologic pattern that affects
women more than men and this form may occur alone or with typical LP lesions
elsewhere.
LPP can be subdivided into three variants: (1) classic
LPP, (2) frontal fibrosing alopecia, and (3) Lassueur–Graham–Little–Piccardi
syndrome.
In classic LPP, individual keratotic follicular papules
surrounded by a narrow violaceous rim that coalesce to form plaques with subsequent hair loss resulting in patchy scarring
alopecia of scalp are usually seen. The
inflammatory process may result in scarring and loss of follicular structure,
i.e. a permanent alopecia. Perifollicular erythema and acuminate keratotic
plugs are characteristic features. Lichen planopilaris resulting in atrophic,
scarred, porcelain-colored area centrally with most active lesions consisting
of acuminate keratotic
follicular plugs and perifollicular scaling
along with perifollicular erythema, are found at the margins of alopecia
patches and follicular convergence resulting in doll's hair formation.
Follicular-centered lesions are usually observed under close inspection of the
scalp and orifices, particularly at the margins of the alopecic area or within
patches still bearing hair. Dermatoscopic features of LPP include absence of
follicular opening, cicatricial white patches, perifollicular casts and
perifollicular scale, blue gray dots, perifollicular erythema and polytrichia
(two or three hairs).
A variant of lichen planopilaris known as Graham
Little–Piccardi–Lassueur syndrome is characterized by the triad of: progressive patchy cicatricial alopecia of the
scalp,
non scarring alopecia of axillae, pubic area, and eyebrows as well as grouped
spinous follicular papules resembling lichen spinulosus or keratosis pilaris on
the trunk and extremities.
Frontal fibrosing
alopecia is an uncommon condition characterized by progressive frontotemporal
recession due to inflammatory destruction of hair follicles. Up to 75% of women
with FFA report concomitant loss of the eyebrows,
which tends to be non-inflammatory. It is more common in postmenopausal women.
It may be associated with mucocutaneous lichen planus.
Pseudopelade of Brocq
is a rare clinical syndrome of scarring alopecia and fibrosis, in which
distinct pathologic features are absent. It is generally accepted that
pseudopelade of Brocq is the end stage of follicular fibrosis caused by a
primary inflammatory dermatosis such as lichen planus, lupus erythematosus,
pustular-scarring forms of folliculitis.
Mucosal Lichen Planus
Lichen planus can affect the mucosal surfaces of mouth,
vagina, esophagus, conjunctiva, urethra, anus, nose, and larynx.
ORAL LP
OLP
is probably about eight times more common than cutaneous lichen planus. The
disease develops in women more than twice as often as in men and most commonly
occurs in the fifth to sixth decade of life, although the disease can sometimes
affect children. Oral involvement is observed in up
to 75% of patients with cutaneous LP, but the former can be the only
manifestation of the disease, and oral lesions may precede, accompany or follow lesions
elsewhere.
In patients
whose initial presentation is oral LP will eventually develop cutaneous LP in
approximately 15% and vulvar and/or vaginal involvement in 25%. However, scalp,
nail, esophageal and ocular involvement are uncommon. Whereas cutaneous lesions
of lichen planus (LP) are self-limiting and pruritic, oral lesions are chronic,
rarely undergo spontaneous remission, potentially premalignant, often a source
of morbidity and difficult to palliate.
Etiology
Most
oral lichen planus is idiopathic but significantly greater anxiety and
depression are observed among patients with oral lichen planus compared with
controls. Lesions clinically and histologically similar, termed ‘lichenoid
lesions’, are sometimes caused by dental restorative materials, (e.g. chromate,
gold and thimerosal), chronic GVHD, drug use (e.g. non‐steroidal anti‐inflammatory agents), diabetes or chronic liver disease,
especially chronic active hepatitis due to HCV infection.
Clinical
features
OLP may
manifest in one of three clinical forms: 1) reticular, including raised
hyperkeratotic papules and plaques; 2) erythematosus, including atrophic
lesions; and 3) erosive, including ulcerated and bullous lesions. Reticular
lesions, the most recognized form of OLP, often occur as isolated lesions and
may be the only clinical manifestation of the disease. They
are often symptomless but may cause soreness. Erythematous lesions are
accompanied by reticular lesions, and erosive lesions are accompanied by both
reticular and erythematous lesions in almost all cases. This feature helps
clinically differentiate OLP from other diseases such as pemphigus and
pemphigoid, which are characterized by isolated areas of erythema and/or
erosions. Erythematous and erosive lesions result in varying degrees of pain as
well as burning, swelling, irritation, and bleeding with brushing.
The
diagnosis of OLP can be made from the clinical features if they are
sufficiently characteristic, particularly if typical skin lesions are also
present, but biopsy is recommended to confirm the diagnosis.
OLP develops
most frequently on the posterior buccal mucosa followed by the tongue, gingiva,
labial mucosa, and vermilion of the lower lip. Lesions on the palate, floor of
the mouth, and upper lip are uncommonly observed. The reticular pattern is
characterized by slightly raised whitish linear lines in a lace-like pattern or
in rings with short radiating spines (wickham striae). The striae often display
a peripheral erythematous zone, which reflects sub epithelial inflammation.
Lines are wavy and parallel. The most common site of involvement is the posterior
buccal mucosa; lesions are often bilateral and symmetric. On the tongue, the
lesions are usually in the form of fixed, irregular white plaques, often
slightly depressed below the surrounding normal mucous membrane, especially on
the upper surface and edges. Reticular OLP can sometimes be observed at the
vermillion border of the lip. There may be striking pigmentation of oral LP in
darkly pigmented races.
There is a higher incidence of
plaque-like lesions among tobacco smokers called smoker’s patches’, which
characteristically involve the palate.
Approximately
10% of patients with OLP have the disease confined to the gingiva and present
as raised white lacy lesions or more commonly as desquamative gingivitis,
typically with atrophic and erosive lesions. On the other hand, lichen planus
is the most common cause for desquamative gingivitis. Direct immunofluorescence
is an effective method of excluding other causes of desquamative gingivitis
that share similar clinical features with OLP, including pemphigus, pemphigoid,
linear IgA disease and foreign body gingivitis. Diabetes is a possible
associated disease of oral LP, and candidiasis may coexist with LP in some
patients.
Erosive lichen planus,
which frequently affects the dorsum and lateral borders of the tongue or the
buccal mucosae on both sides, is uncommon. The erosions are often large,
slightly depressed or raised with a yellow slough, and have an irregular
outline, but they are not always as painful as might be imagined. The
surrounding mucosa is often erythematous and glazed in appearance, with loss of
filiform papillae of the tongue, and there are often pathognomonic whitish
striae. It
has been reported that the erosive oral LP is less frequently associated with
cutaneous LP than are all other types of oral LP. Such mucous membrane lesions
are more therapy-resistant and less likely to spontaneously remit than
cutaneous lesions. Malignant transformation of longstanding, non-healing ulcerative lesions in the mouth has been reported,
but it must be distinguished from pseudoepitheliomatous hyperplasia. The WHO has defined oral LP as a “premalignant condition”
because of this risk.
Oral lichenoid reaction is similar
clinically and histologically to oral lichen planus, however, with identifiable
etiology. Differentiating these two entities is often difficult. Oral lichenoid
reactions may be asymmetrical on the buccal mucosa and occur adjacent to dental
amalgam restorations, especially fillings that are worn and cracked. If patch
testing reveals mercury allergy, changing to another type of filling may prove
beneficial.
Very
occasionally, LP lesions extend to the larynx or esophagus. Esophageal lichen
planus is rare and affects the proximal esophagus. It manifests as progressive
dysphagia and odynophagia. Endoscopic findings can include lacy white papules,
pinpoint erosions, desquamation, pseudo membranes, and stenosis.
Histologically, it shows parakeratosis, epithelial atrophy, and lack of hypergranulosis.
Squamous cell carcinoma of esophagus may develop after longstanding disease.
Several studies have reported a relationship between oral
LP and chronic liver disease, particularly that due to HCV infection. Some
authors found an association of HCV with the reticular and plaque forms,
whereas other authors reported an association of HCV with the erosive type. In
the HCV-positive oral LP group, oral lesions are more frequently located on the
tongue, labial mucosa and gingivae.
Modified World Health Organization diagnostic criteria of
OLP
CLINICAL
CRITERIA
ØPresence of bilateral, more or less
symmetrical lesions
ØPresence of a lacelike network of slightly
raised gray- white lines (reticular pattern)
ØErosive, atrophic, bullous and plaque-type
lesions are accepted only as a subtype in the presence of reticular lesion
elsewhere in the oral mucosa
ØIn all other lesions that resemble OLP but do
not complete the aforementioned criteria, the term “clinically compatible with”
should be used
HISOPATHOLOGIC
CRITERIA
ØPresence of a well-defined band like zone of
cellular infiltration that is confined to the superficial part of the
connective tissue, consisting mainly of lymphocytes
ØSigns of liquefaction degeneration in the
basal cell layer
ØAbsence of epithelial dysplasia
ØWhen the histopathologic features are less
obvious, the term “histopathologically compatible with” should be used
Male genitalia
Male genitalia are involved in 25% of cases, and the
glans penis is most commonly affected, with annular lesions frequently present.
Other sites commonly affected are shaft of the penis, prepuce and scrotum. Anal
lesions of mucosal lichen planus present with leukokeratosis, hyperkeratosis,
fissuring, and erosions.
Vulvovaginal LP
Lesions on the female genitalia may
occur alone, be combined with lesions in the mouth only, or be part of
widespread involvement. The clinical presentation of LP of the vulva spans a
spectrum from subtle, fine, reticulate papules to severe erosive disease
accompanied by dyspareunia, scarring and loss of the normal vulvar
architecture. Vaginal
involvement occurs in up to 70% of women with erosive vulvar LP.
Diagnostic criteria have been
proposed recently and include:
· Well‐demarcated erosions or glazed erythematous areas at the
vaginal introitus
· The presence of a hyperkeratotic white border to erythematous
areas/ erosions and/or Wickham's striae in the surrounding skin
· Symptoms of pain/burning
· Scarring/loss of normal architecture
· Presence of vaginal inflammation and
· Involvement of other mucosal sites.
The association of erosive LP of the
vulva and vagina with desquamative gingivitis has been termed the vulvo‐vaginal–gingival syndrome.
Lichen planus of the palms and soles
Lichen
planus of the palms and soles generally occurs as an isolated phenomenon, but
may appear simultaneously with disease in other areas. Lesions on the palms and soles are uncommon, lack the
characteristic shape and color of lesions elsewhere. The lesions differ
from classic lesions of lichen planus in that the papules are larger and
aggregate into semi translucent plaques with a globular waxy surface and are firm to the touch and yellow in hue. Itching may be absent.
Ulcerations can occur within palmoplantar lesions of LP,
particularly those on the soles
of one or both feet, often recalcitrant to conventional
therapy. Although palmoplantar LP is
more common in men than in women, ulcerative LP prevails in female patients.
The ulcers are large and intensely painful with
gradual, permanent loss of the toenails; there may be secondary webbing of the
toes. Chronic ulcerative lesions are at risk of
developing squamous cell carcinoma.
Lichen Planus of the nails
The nails are affected in ~10% of patients with LP and usually
several nails are affected.
Fingernails are more frequently affected than toenails, with initial
involvement of two or three fingernails before subsequent involvement of the
remaining digits. There are three major forms
of nail LP: classic nail
lichen planus, Trachyonychia
(twenty-nail dystrophy) and Idiopathic atrophy of
the nails. The characteristic nail abnormalities
include lateral thinning, longitudinal ridging, and fissuring. These changes
are manifestations of matrix damage, which can lead to scarring and dorsal
pterygium formation if left untreated. Nonspecific changes in the nail bed
include yellow discoloration, onycholysis, and subungual hyperkeratosis. Details
are described in the chapter of Nail disorders.
Inverse Lichen Planus
In this unusual variant, an inverse
distribution pattern is observed. Pink to violaceous papules and plaques appear
in intertriginous zones (axillae > inguinal and inframammary folds) and less
often in the popliteal and antecubital fossae. Occasionally, there are LP
lesions elsewhere on the body. Hyper pigmentation is usually present as well
and it may be the sole manifestation, leading to overlap with LP pigmentosus.
Special Forms of Lichen Planus or Lichenoid Eruptions
Lichenoid drug eruption (drug-induced LP)
Lichen planus-like or lichenoid eruptions describe a
group of cutaneous reactions identical or similar to lichen planus. Lichenoid
drug eruptions have been reported after ingestion, contact, or inhalation of
certain chemicals. Despite the significant overlap between LP and lichenoid
drug eruption, there are both clinical and histologic clues that favor one
diagnosis over the other. Both sexes are equally affected, but lichenoid drug
eruptions tend to occur in adults approximately 10 years older than those with
idiopathic LP.
|
FEATURES FOR DISTINGUISHING LICHENOID DRUG ERUPTION FROM LICHEN
PLANUS |
||
|
|
Lichenoid drug eruption |
Idiopathic lichen planus |
|
Mean age |
66 years |
50 years |
|
Location |
More generalized; often spares the “classic” sites of
LP |
Wrists, flexor forearms, presacral, lower legs,
genitalia |
|
Morphology |
More eczematous, psoriasiform or pityriasis rosea-like |
Shiny, flat-topped, polygonal, violaceous papules |
|
Wickham's striae |
Uncommon |
Present |
|
Hyper pigmentation |
Very common, sometimes persistent |
Common |
|
Photo distribution |
Frequent* |
Unusual |
|
Mucous membranes |
Usually spared |
Often involved |
|
Histology |
Varying degree of eosinophilic and/or plasma cell
infiltrates |
Eosinophils and plasma cells uncommon |
|
Deep infiltrate may be present |
Dense band-like infiltrate of lymphocytes |
|
|
Parakeratosis |
No parakeratosis |
|
|
* |
Especially with medications such as
hydrochlorothiazide. |
Mixed’ lichen planus/discoid lupus
erythematosus disease patterns
This is a rare variant characterized by patients whose lesions have overlapping features of both LP
and lupus erythematosus (LE). Atrophic plaques and patches with hypo
pigmentation and a livid red to blue–violet color with telangiectasia and
minimal scaling are characteristic. Transient bullae may develop. Classic
lesions of lichen planus, photosensitivity, pruritus, and follicular plugging
are not common. Lesions may develop anywhere, but are
preferentially located in acral sites. This disease variant is
characterized by a prolonged course and lack of response to treatment. Histologic and direct immunofluorescence (DIF) microscopic
findings show features of both LP and LE. Histologically, a lichenoid
reaction typical for lichen planus and histologic features of lupus
erythematosus are usually present in the same biopsy. By direct
immunofluorescence, cytoid bodies staining with IgG, IgM, and C3
intraepidermally or at the dermal–epidermal junction, as seen in classic lichen
planus, are most common. Linear to granular deposition of IgM and C3 (as seen
in lupus erythematosus, but not in lichen planus) and shaggy deposition of
fibrinogen at the basement membrane zone, typical of lichen planus are observed
occasionally. Whether systemic immunologic
abnormalities such as high titers of ANA are present in these patients is
controversial, but case reports suggest that some patients have disease at the
chronic cutaneous LE end of the clinical spectrum while others meet the
criteria for systemic LE.
Lichen planus, bullous and pemphigoides
In bullous LP, vesicles
and bullae develop within pre-existing lesions of LP as a result of intense
lichenoid inflammation and severe
liquefaction degeneration of the basal cell layer. This leads to
epidermal–dermal separation, i.e. exaggerated Max-Joseph spaces. Histologically, there is sub epidermal bulla formation with
typical changes of LP, and direct and indirect IMF is negative. The eruption is
usually only of short duration. In contrast, patients with LP pemphigoides have circulating IgG
autoantibodies directed against the 180 kDa BP antigen (BP180; BPAG2), as in
idiopathic BP. In this variant, the LP tends
to be acute and generalized and is followed by the sudden appearance of large tense
bullae both within LP lesions and previously uninvolved skin, but the
diagnosis of LP usually precedes the LP pemphigoides. LP pemphigoides has been precipitated by psoralen and UVA
(PUVA) and has evolved into pemphigoid nodularis. In LP pemphigoides, the
histology shows a subepidermal bulla with no evidence of associated LP. Direct
IMF shows linear basement membrane zone deposition of IgG and C3 in
perilesional skin. Immunoelectron microscopic studies reveal deposition of IgG
and C3 in the base of the bulla and not in the roof as found in bullous
pemphigoid.
Immunoblotting data have revealed that circulating autoantibodies in LP pemphigoides react with an epitope within the C‐terminal NC16A domain of bullous pemphigoid 180 kDa antigen. To date, no reactivity against the 230 kDa BP antigen, type VII collagen, or the laminin-5 subunits has been detected. It seems that damage to the basal layer by a lichenoid infiltrate may expose hidden basement membrane antigens to the autoreactive T cells, leading to the formation of auto antibodies and subepidermal bullae. The mean age of patients with LP pemphigoides is lower than that of those with classic bullous pemphigoid, and the course of the disease also tends to be less severe.
Acute and subacute lichen planus with a
confluence of lesions
Lichen
planus may occur abruptly as a generalized, intensely pruritic eruption.
Initially, the papules are pinpoint, numerous, and isolated. The papules may
remain discrete or become confluent as large, red, eczematous-like, thin
plaques. A highly characteristic, diffuse, dark brown, post inflammatory
pigmentation remains as the disease subsides. Lichenoid drug eruptions are
frequently of this diffuse type. Low-grade fever may be present in the first
few days, and lesions appear on the trunk and extremities. The disease is
seldom seen on the face or scalp and is rare on the palms and soles. Successive crops may
occur. The clinical course is
usually self-limited, and in general lesions resolve within 3 to 9 months.
Lichen Planus and
Malignant Transformation
It is currently believed that the risk of malignant
transformation is fairly low. Risk factors that increase the likelihood of
developing oral cancer are long-standing disease, erosive or atrophic types,
tobacco use, and possibly esophageal involvement. It is generally accepted that
about 2% of patients with oral lichen planus develop SCC. The majority of these
cases are in situ carcinoma or with micro invasive pattern. The most common
site for cancer is the tongue, followed by buccal mucosa, gingiva, and, rarely,
the lip. Clinically, the lesions appear as indurated, nonhealing ulcers, or
exophytic lesions with a keratotic surface. Red atrophic plaques could also be
seen and often correlate with SCC in situ. Advanced cases could result in nodal
metastases and occasionally death.
The risk of skin malignancy in cutaneous lichen planus is
extremely low. Most patients developing SCC in cutaneous lichen planus had a
history of either arsenic or X-ray exposure.
Laboratory
tests to consider for LP
·
Complete
blood count
·
Patch
testing, particularly for oral LP
·
Lipid
panel
·
Thyroid
function tests for lichen planopilaris
·
Antithyroid
peroxidase antibodies
·
Antithyroglobulin
antibodies
·
Hepatitis
c virus testing for oral LP
Patch tests in
patients with oral lichen planus usually reveal positive results in a majority
of patients. Sensitivity to mercury and gold is often positive in one-half of
the cases. Avoidance of these clinically
relevant sensitizers results in amelioration of disease. Dyslipidemia is more
common in patients with lichen planus.
Histopathology
Microscopic features: Orthokeratoic hyperkeratosis, wedge shaped hypergranulosis and saw-tooth appearance of the epidermis.
Effacement of the dermoepidermal junction by band-like mononuclear inflammatory cell infiltrate.
Hydropic degeneration of basal cells; Colloid body formation; Pigment incontinence.
Despite its different clinical manifestations, the
histopathology of LP is fairly uniform and
is the most useful investigation to confirm a diagnosis of LP. The primary features are hyperkeratosis
without parakeratosis, focal increases in the granular cell layer, irregular
acanthosis with a “sawtooth” appearance, liquefactive degeneration of the basal
cell layer, and a band-like lymphocytic infiltrate at the dermal–epidermal
junction. A focal
increase in thickness of the granular layer and infiltrate corresponds to the
presence of Wickham's striae. Degenerating basal epidermal cells are
transformed into colloid bodies (also referred to as
Civatte, hyaline or cytoid bodies),
which appear singly or in clumps and are usually present in the
lower levels of the epidermis and the superficial dermis. Vacuolar changes
within the basal cell layer may become confluent and result in small
separations between the epidermis and the dermis (called “Max-Joseph spaces”).
There is often incontinence of pigment with multiple dermal melanophages.
The
histopathology of oral LP is similar to that of cutaneous lichen planus,
although saw tooth rete ridges are rarely seen in oral biopsies. Oral
LP lesions often show parakeratosis rather than hyperkeratosis, and the
epidermis frequently becomes atrophic.
Lesions of lichen planopilaris are
characterized by an inflammatory cell infiltrate around the hair follicles even
at an early stage. Most of the inflammation involves the upper
half of the follicle, with the isthmus affected in one-third of patients.
Destruction of the follicles represents a later stage.
In LP pemphigoides, a primary histologic feature of the
bullous lesions is a subepidermal separation with an abundance of eosinophils
(occasionally neutrophil-rich infiltrates), whereas the papular lesions have
the usual features of LP. DIF microscopy of peribullous skin shows linear
deposition of IgG and C3 along the dermal–epidermal junction, similar to BP.
Apoptotic cells, as evidenced by Civatte bodies, tend to
remain in the lower levels of the epidermis in idiopathic LP; in contrast, they
are found in the cornified or granular layer in lichenoid drug eruptions. Direct immunofluorescence shows globular deposits of
immunoglobulin M (IgM) and occasionally IgG and IgA, representing apoptotic
keratinocytes, around the DEJ and lower epidermis, with fibrin deposition at
the region of the DEJ. Although the band-like inflammatory
infiltrate is usually restricted to the papillary dermis in LP and involvement
of the deep vascular plexus suggests a lichenoid drug eruption (though observed
in <50% of cases). In lichen planopilaris lesions, IgM, IgG and IgA are found
in varying combinations along the follicle–dermal interface.
DIF of Lichen Planus showing IgM
positive cytoid bodies in upper dermis.
DIF of Lichen Planus showing
shaggy deposits of fibrinogen at DEJ.
|
The
pattern of DIF results of potential differential diagnoses of lichen planus. |
||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||
|
BMZ: basement membrane zone; DIF: direct
immunofluorescence; Ig: immunoglobulin. |
||||||||||||||||||||||||||||||||||||||
Dermatoscopy
The use of dermoscopy is found useful in some cases when Wickham's striae can be visualized
better with the devise. Typical features of dermoscopy images of LP include a
network of whitish striae with red globules at the periphery.
Prognosis and Clinical
Course
Lichen planus is an unpredictable disease that typically
persists for 1–2 years, but which may follow a chronic, relapsing course over
many years. The duration varies according to the extent and site of involvement
and morphology of lesions. Generalized eruptions tend to have a rapid course
and heal spontaneously faster than limited cutaneous disease. Lichen planopilaris
is one of the most chronic and often progressive disease variants with little
potential for hair regrowth after follicular inflammation and destruction.
Hypertrophic lichen planus typically follows a protracted, unremitting course.
Spontaneous regression is also an uncommon feature of oral lichen planus. The
mean duration for oral lichen planus is 5 years. The reticular variant has a
better prognosis than erosive disease that does not heal spontaneously.
Generally, the duration of disease conforms to the following order, from
shortest duration to longest duration: (1) generalized cutaneous (2)
non-generalized cutaneous, (3) cutaneous + mucous membrane, (4) mucous
membrane, (5) hypertrophic, and (6) lichen planopilaris.
Relapse of disease occurs in 15%–20% of cases and tends
to occur in the same area as the initial episode. Recurrences are more common
in generalized lichen planus and are usually of shorter duration.
Management
Management of lichen planus can be challenging and
discouraging for both the patient and physician. Lichen planus may be
associated with only minor symptoms or may cause considerable discomfort and
disability. Hence, treatment options should be assessed for attendant risks and
benefits and tailored to the extent and severity of disease. Avoidance of
exacerbating drugs and minimizing trauma to skin and mucosal tissues, are
routinely recommended.
Treatment of LP depends on the localization, clinical
form and severity. For
cutaneous LP, the aim of treatment is to reduce pruritus and time to resolution
of the lesions. No treatment is usually recommended for asymptomatic oral LP. However,
painful, erosive LP may need aggressive and long‐term treatments. Nail or scalp involvement, which may induce
scars, genital LP and esophageal and conjunctival involvement, which may induce
strictures and fibrosis, may require rapid treatment to avoid scaring or avoid
a fatal course.
The main therapy for LP is
corticosteroids, commonly recommended as first line treatment for LP.
Cutaneous
lichen planus
|
TREATMENT |
DOSAGE |
COMMENTS |
|
|
High-potency
topical corticosteroids |
Administered twice
daily |
First-line therapy |
|
|
Oral
corticosteroids (prednisone) |
30 to 60 mg daily
for three to six weeks, then dose is tapered over the next four to six weeks |
For severe,
widespread lichen planus |
|
|
Phototherapy |
30- to 40-minute
treatments, two or three times weekly |
For severe disease;
narrow-band ultraviolet B is preferred over psoralen plus ultraviolet A |
— |
note: Acitretin is
used in more severe cases of cutaneous lichen planus that do not respond to
topical treatment; this is an off-label use.
Therapeutic ladder
First line
·
Limited
cutaneous LP: very potent corticosteroids
(clobetasol propionate ointment 0.05%); potent topical corticosteroids can be
used in less severe forms of LP or during maintenance therapy
·
Widespread
cutaneous LP: prednisolone 0.5–1 mg/kg per day
until improvement
Second line
·
Prednisolone 0.5–1 mg/kg per day
until improvement
·
Acitretin 30 mg per day for 8 weeks
·
PUVA or UVB: two to three times a
week, 12 times alone or associated with systemic retinoids
First
line
Topical
corticosteroids are the first line treatment for limited cutaneous LP. The use
of very potent corticosteroids is required (clobetasol propionate ointment
0.05%) once daily at night until remission. If no response is observed after 6
weeks, second line therapy has to be considered. Topical
corticosteroids are particularly popular for children. For hypertrophic LP, very potent
corticosteroids need to be applied under an occlusive bandage.
Intralesional triamcinolone acetonide (5–10 mg/mL) is
effective in treating resistant cutaneous lichen planus. This may also be used
in lichen planus of the nails with injection of the proximal nail fold every 4
weeks. Regression of lesions occurs within 3–4 months. For hypertrophic lichen
planus, higher concentrations of intralesional triamcinolone acetonide (10–20 mg/mL) may
be required. Regular and close observation should be performed to monitor for
any signs of atrophy or localized hypo pigmentation that should prompt
cessation of therapy. Intralesional injection is of special value in lichen
planopilaris.
Oral
corticosteroids are the first line treatment for widespread cutaneous LP: the
minimal effective daily dose of prednisone for treating LP is greater than 20
mg/day (e.g., 30–80 mg prednisone) for 2–6 weeks with
subsequent taper over 4–6 weeks. Rebound and relapses may occur, but long-term
maintenance therapy with systemic corticosteroids should be avoided.
Second
line
Retinoids
Acitretin is the only systemic retinoid that has a
relatively good level of evidence regarding its efficacy in the treatment of
cutaneous LP. Acitretin 1 mg/kg per day is helpful as adjunctive measure in
severe (oral, hypertrophic) cases, but usually additional topical treatment is
required. A therapeutic regimen consisting of acitretin 30 mg/day for 8
weeks resulted in significant improvement and marked remission is achieved in
the treatment group. Retinoids tend to be used for recalcitrant cases, and,
therefore, relapses may occur after discontinuation of the drug; as a result,
long-term maintenance therapy may be required. Considering the side effects of teratogenicity and
mucocutaneous dryness, acitretin is used as second line therapy in cutaneous
LP. In case reports, alitretinoin, up to 25 mg/day for 4 weeks, was
reported to clear oral, esophageal and cutaneous LP.
Phototherapy
In patients with resistant
longstanding LP, significant improvement has been observed after systemic or bath
PUVA. However, the risk of promoting carcinogenesis, especially in patients
with skin types I and II, has to be balanced against the benefits. Psoralen and
ultraviolet A (PUVA) light photo chemotherapy is usually successful in
generalized cutaneous lichen planus. PUVA phototherapy may also be combined
with acitretin. Trioxsalen, 50 mg added to 150 L of water, then exposing the
patients to UVA after 10 minutes of bathing gave good results. For generalized
disease, clearance within a mean of 3 months was observed in 70% of patients
treated with narrow‐band
UVB therapy. Phototherapy can increase the risk of residual hyper pigmentation
in dark‐skinned patients. Phototherapy has been used in
conjunction with oral glucocorticoids to hasten the response.
Third
line
Immunosuppressive Agents
Oral cyclosporine has been used successfully
in inducing remission in severe cases of LP resistant
to systemic retinoids and corticosteroids. Complete responses were observed
with doses of cyclosporine ranging from 1 to 6 mg/kg/day. Pruritus
usually disappears after 1–2 weeks. Clearance of the rash is seen in 4–6 weeks.
Adverse effects as well as relapse after discontinuation of the drug, limit its
use to severe cases.
Azathioprine is useful in recalcitrant,
generalized cutaneous lichen planus and in lichen planus pemphigoides.
Based upon a case series, weekly low-dose methotrexate is of value in generalized LP. A complete
response was achieved in 10 of 11 patients within 1 month and the medication
was well tolerated without adverse effects.
Mycophenolate mofetil, an immunosuppressive agent which specifically and reversibly
inhibits the proliferation of activated T cells, is reported to be effective in
the management of disseminated, erosive, hypertrophic and bullous variants of LP.
It is also effective at reducing the signs and symptoms of active
lichen planopilaris in 83% of patients who had failed multiple prior treatments.
It may be preferable to other immunosuppressive drugs
such as cyclosporine because of its safer side-effect profile.
Miscellaneous
Hydroxychloroquine is effective in decreasing symptoms
and signs in Lichen planopilaris and its variant frontal fibrosing alopecia in
69% and 83% of patients after 6 and 12 months of treatment, respectively. It is
also the main treatment in actinic lichen planus at 200–400 mg/day in addition
to sun protection.
Oral metronidazole 500 mg twice daily for 1–2
months also reportedly clears the majority of cases of generalized lichen
planus.
Based on the benefit in bullous pemphigoid, combination
therapy with tetracycline or doxycycline and nicotinamide has been reported as useful
in the treatment of lichen planus pemphigoides. Tetracycline should be
considered in lichen planopilaris.
An open-label pilot study of apremilast, a novel
oral phosphodiesterase IV inhibitor, in 10 patients with moderate to severe LP
demonstrated statistically significant clinical improvement in all of the
patients after 12 weeks.
Oral
lichen planus
Treatment ladder
First line
·
Symptomatic
oral LP: very potent corticosteroids
(clobetasol propionate ointment 0.05%) three times daily until remission, then
maintenance therapy
·
Potent topical corticosteroids can
be used in less severe forms of LP or during maintenance therapy: soluble
prednisolone tablets, 5 mg in 15 mL water for mouthwash three times daily for
widespread oral LP. An alternative to
prednisolone tablets is betamethasone soluble tablets (Betnesol) 0.5 mg
·
Severe erosive
LP: prednisolone 0.5–1 mg/kg per day
until improvement
Second line
·
Papular and
plaque‐like white forms and in absence of erosive lesions: topical retinoids (retinoic acid or isotretinoin
lotion/gel 0.1%) twice daily
·
Resistant to
topical corticosteroids: prednisolone
0.5–1 mg/kg per day until improvement
Third line
·
Cortico‐dependent or cortico‐resistant
erosive LP: systemic immunosuppressive agents
(e.g. azathioprine, mycophenolate mofetil, methotrexate, oral and topical
ciclosporin)
General Measures
Treatment
is not always necessary, unless there are symptoms. Unfortunately, although the
natural history of cutaneous lichen planus is one of remission in most cases,
oral lichen planus rarely remits, and thus treatment is indicated for
symptomatic oral lichen planus.
The aims of
treatment are to heal erosive lesions in order to reduce pain and permit normal
food intake. Education of the patient should emphasize that oral LP frequently
has a chronic course marked by treatment‐induced remission followed by
relapse. Considering the potential higher risk of squamous cell carcinoma, the
need for regular clinical surveillance on a long‐term basis has also to be explained.
Predisposing
factors should be corrected. Replacement of amalgam or gold dental
restorations with composite material is frequently of considerable benefit in
patients with oral lichenoid reactions, even in the apparent absence of
relevant patch test results. Chronic lesions on the buccal mucosa in contact
with metal or other contact sensitizers frequently heal promptly after
replacement. Occasionally, lesions at sites distant to oral lesions may also
clear after removal of metal restorations. Gingival lesions may respond less
favorably. If
drugs are implicated, the physician should be consulted as to possible changes
in therapy. If there is diabetes or HCV infection, this should be treated by a
physician. Good oral hygiene and regular personal and professional
dental care need to be encouraged. Alcohol
and tobacco as well as spicy or acidic foods and drinks should be avoided.
First line
Topical Steroids
Topical
corticosteroids are the first line treatment for symptomatic oral LP. Use
of occlusive materials suitable for mucous membranes, such as Orabase, may
provide protection, sustained tissue contact with the medication, and alleviate
the discomfort associated with erosive lesions. In the absence of specific
available formulation for oral lesions, super potent corticosteroids (0.05%
clobetasol propionate ointment) can be applied three times daily with a gloved
finger on erosive lesions. It
is recommended to not drink or eat for 1 h after the application.
Alternatively, for widespread, less severe lesions or maintenance therapy, a
patient can use a soluble prednisolone tablet 5 mg dissolved in 15 ml water for
a mouthwash swish and rinse three times daily. Oral candidiasis is the most
frequent complication of this treatment. The use of chlorhexidine gluconate mouthwashes and
topical anticandidal medications is recommended during therapy.
Topical retinoids
For papular and
plaque‐like forms of oral LP, topical
retinoids (tretinoin gel) can
be recommended as first line treatment. Isotretinoin gel is also effective,
especially in nonerosive oral lesions. However, recurrence is common after
discontinuation of therapy. Topical retinoids are often used in conjunction
with topical glucocorticoids.
Second line
If no or insufficient improvement is
observed after 6 weeks of topical corticosteroids and for severe case of
erosive LP associated with eating difficulties and eventual weight loss, oral
corticosteroids can
be used alone, or, more commonly, in conjunction with topical glucocorticoids. Prednisone dose 0.5 -1mg/kg day,
until remission, generally 4–6 weeks
and then tapered
over the next 3–6 weeks, or Betamethasone 5 mg on two
consecutive days per week show benefit. Relapses are common after dose
reduction or discontinuation. Slow
reductions in dose are needed because of the risk of relapse.
Two-thirds of
patients showed marked improvement or complete remission within 8 weeks of
instituting acitretin, 30 mg/day in
erosive OLP.
Third line
Tacrolimus and
Pimecrolimus
Tacrolimus, effective in erosive
mucosal disease, provides rapid relief from pain and burning with minimal side
effects. It is at least equally effective to clobetasol propionate 0.05% ointment and triamcinolone acetonide 0.1% paste in the
treatment of oral lichen planus.
Pimecrolimus 1% cream was shown to be as
effective as triamcinolone acetonide 0.1% paste in
treating oral lichen planus, and proved to be effective in treating vulvar
disease.
Current US Food and Drug
Administration (FDA) labelling states that topical pimecrolimus and tacrolimus
should not be used to treat premalignant conditions. They have to be used with
caution in oral LP due to the inherent risk of malignant transformation.
Mild lichen planus
Topical corticosteroids
are the mainstay of therapy (e.g. triamcinolone acetate, betamethasone or
fluocinolone). Erosive and gingival lesions are often recalcitrant. Next, high‐potency corticosteroids such as clobetasol,
fluocinonide or fluticasone may be employed initially and then changed to a
lower potency drug.
Moderate lichen planus
If there is severe or
extensive oral involvement, topical ciclosporin or tacrolimus may be of
significant benefit, often being used with a high‐potency or super‐potent topical steroid such as clobetasol,
fluticasone or mometasone. Topical creams or pastes can be applied in a
suitable customized tray or veneer to be worn at night. This regimen is useful
in the management of lichen planus‐related desquamative gingivitis recalcitrant to
other therapies.
Severe lichen planus
In severe lichen planus
in multiple sites, patients may require systemic corticosteroids, azathioprine,
cyclophosphamide, hydroxychloroquine, acitretin, thalidomide or ciclosporin.
Dapsone is occasionally effective.
Non‐reticular lichen planus
Patients with non‐reticular lichen planus should be monitored to
exclude development of carcinoma; tobacco and alcohol use should be minimized.
Ano‐genital lichen planus
Early super‐potent corticosteroid treatment (0.05% clobetasol propionate
ointment once daily) aims to resolve symptoms and prevent synechiae and
scarring of the genital area. Potent corticosteroids can be used daily during
the initial phase until symptom resolution. Foreskin retraction or removal
surgery in uncircumcised men and vaginal dilators in women are used to prevent
synechiae formation. Surgery is required after complete resolution of the
active lesions if adhesion occurs.
Lichen planopilaris
In order to lessen pain and
pruritus, and to avoid irreversible alopecia, first line treatment is potent
corticosteroids (e.g. 0.05% clobetasol propionate ointment twice daily). In
severe cases or in cases of insufficient improvement after corticosteroid
ointment, second line treatment is monthly intralesional injection of
triamcinolone acetonide (0.5–10 mg/mL) or oral corticosteroids (prednisolone 1
mg/kg/day).
|
Proposed
treatment strategy for classic lichen planopilaris. Notes: *Topical/intralesional steroids may be added to systemic therapies in the
case of persistence of limited active areas. §A short course of systemic steroids should be
considered only to halt the progression and to improve symptoms in rapidly
progressive and severe cases. |
Frontal fibrosing
alopecia
Treatments can be of limited
efficacy and includes topical and intralesional corticosteroids, antibiotics,
hydroxychloroquine, topical and oral immunomodulators and 5α‐reductase inhibitors.
Nail lichen planus
The aims of treatment are to reduce
pain and avoid irreversible nail scars. Intramuscular injection or oral
systemic glucocorticoids and/or intralesional injection or topical
glucocorticoids are commonly used.
When three or less than three nails
are involved, the recommended treatment is a twice daily application of super‐potent corticosteroids (e.g. 0.05% clobetasol propionate
ointment), or if lesions are more severe, monthly intralesional injection of
triamcinolone acetonide (0.5–10 mg/mL) in the periungual sites.
When more than three nails are
involved, systemic corticosteroids are required. Treatment with oral
prednisolone (0.5–1 mg/kg/day) for 4–66 weeks or intramuscular triamcinolone
acetonide injection has been reported.
Severe erosive lichen planus
Systemic corticosteroids are first
line treatment. Systemic immunosuppressive agents (e.g. azathioprine,
mycophenolate mofetil and methotrexate) are used as corticosteroid‐sparing agents for patients with erosive or potentially
scarring LP requiring prolonged systemic corticosteroids or in disease
unresponsive to corticosteroids.
Mixed’ lichen planus/discoid lupus
erythematosus disease patterns
Both ciclosporin and acitretin can
be of benefit in treating LP/DLE overlap syndrome.
Actinic lichen planus
Actinic LP has been treated with
acitretin and topical corticosteroids and with ciclosporin.
Bullous lichen planus and lichen planus pemphigoides
Some cases require treatment with
systemic steroids or azathioprine. A combination of corticosteroids and
acitretin has been used.
