Lichen planus described by Erasmus Wilson in England.
Common in children and adults.
Mucocutaneous condition, affecting the skin, mucosa, genitalia, and confirmmed by Biopsy.
INTRODUCTION — Lichen planus is an uncommon disorder of unknown cause that most commonly affects middle-aged adults. Lichen planus may affect the skin (cutaneous lichen planus), oral cavity (oral lichen planus), genitalia (penile or vulvar lichen planus), scalp (lichen planopilaris), nails, or esophagus.
EPIDEMIOLOGY — The epidemiology of lichen planus is not well-defined. Based upon limited data, cutaneous lichen planus is estimated to occur in less than 1 percent of the population
[
1].
Cutaneous lichen planus most frequently develops between the ages of 30 and 60 years [
1,2]. Childhood cutaneous lichen planus occurs, but is uncommon [
3]. There does not appear to be a strong sex or racial predilection for cutaneous lichen planus [
1,2].
ETIOLOGY — The etiology of lichen planus is not known. An immune-mediated mechanism involving activated T cells, particularly CD8+ T cells, directed against basal keratinocytes has been proposed [
4]. Upregulation of intercellular adhesion molecule-1 (ICAM-1) and cytokines associated with a Th1 immune response, such as interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-6, and IL-8, may also play a role in the pathogenesis of lichen planus [
4-7].
Hepatitis C virus — The association of hepatitis C virus (HCV) with lichen planus is controversial, and a cause and effect relationship is uncertain. A meta-analysis of primarily case-control studies conducted in a number of countries found a statistically significant association between HCV and lichen planus. Compared with control patients, the prevalence of HCV exposure was greater among patients with lichen planus (OR 5.4, 95% CI 3.5-8.3) [
8]. A systematic review also identified an increase in the proportion of lichen planus patients that were HCV positive compared with controls (OR 4.80, 95% CI 3.25-7.09) [
9]. However, subgroup analysis in both studies revealed that the strength of this association varied geographically, and was not statistically significant in all locations. Estimates of the prevalence of HCV infection among patients with oral lichen planus vary widely; studies have reported prevalence rates from 0 to 62 percent [
10].
Clinicians should have a high suspicion for lichen planus in patients with hepatitis C who present with clinical features suggestive of the diagnosis. The meta-analysis cited above found that patients with HCV had an increased prevalence of lichen planus compared to controls (OR 2.5, 95% CI, 2.0-3.1) [
8]. In a study from Italy, among 178 adults with HCV antibodies, five (2.8 percent) had oral lichen planus [
11]. There are also reports of the development or exacerbation of lichen planus during interferon treatment for chronic HCV; the lesions improved when interferon was stopped [
12].
Screening for HCV — Routine screening for HCV infection in patients diagnosed with lichen planus is controversial. The variability in the prevalence of hepatitis C among patients with lichen planus in different geographic locations is likely to influence screening recommendations [
8,9,13-15].
In a United States study in which 195 patients with oral lichen planus were prospectively screened for liver abnormalities, no liver abnormalities or antibodies to hepatitis B or C were detected [
13]. This report suggested that routine screening for HCV is not necessary. Others have suggested screening for HCV in patients diagnosed with lichen planus, particularly those with risk factors for HCV infection, due to the risks of morbidity and transmission that exist with HCV infection and the presence of evidence suggesting an association between lichen planus and HCV [
8,9,15,16].
Further studies are necessary to determine the value of HCV screening in the management of lichen planus patients.
CLINICAL FEATURES — Lichen planus may affect the skin, mucous membranes (especially the oral mucosa), scalp, nails, and genitalia [
1].
Cutaneous lichen planus — The classic presentation of cutaneous lichen planus is a papulosquamous eruption characterized by the development of flat-topped, violaceous papules on the skin (
picture 1A-D). Often, the clinical manifestations are described as the four “P’s:”
●Pruritic
●Purple (actually a slight violaceous hue)
●Polygonal
●Papules or plaques
Individual papules are usually a few millimeters in diameter, but may coalesce to form larger plaques [
2]. With close inspection, fine white lines may be visible on the surface of papules or plaques of cutaneous lichen planus (
picture 2). These lines are described by the term “Wickham’s striae” [
17].
The extremities, particularly the ankles and the volar surface of the wrists, are common sites for cutaneous involvement [
4]. Involvement of the trunk or generalized involvement also can occur (
picture 3). Rare Blaschkoid (
picture 4 and
figure 1) [
18-20], zosteriform [
21-24], and inverse (intertriginous) [
2] distributions of cutaneous lichen planus have been observed.
Patients with lichen planus may exhibit the Koebner reaction (the development of skin lesions in sites of trauma). The Koebner reaction most often occurs as a result of scratching (
picture 5).
The pruritus associated with cutaneous lichen planus often is intense. Asymptomatic eruptions are rare. Lesions often heal with significant postinflammatory hyperpigmentation.
Cutaneous variants — In addition to the classic presentation of cutaneous lichen planus, multiple other clinical presentations of cutaneous disease have been described. Shared histologic findings support the classification of these disorders as variants of cutaneous lichen planus.
Examples of variants of cutaneous lichen planus include [
2]:
●Hypertrophic lichen planus – Hypertrophic lichen planus is characterized by the development of intensely pruritic, flat-topped plaques (
picture 6). The typical site of involvement is the anterior lower legs. Of note, the occasional development of cutaneous squamous cell carcinoma has been reported in patients with longstanding hypertrophic lichen planus lesions [
25].
●Annular lichen planus – Annular lichen planus is characterized by the development of violaceous plaques with central clearing (
picture 7A-C). Although the penis, scrotum, and intertriginous areas are common sites of involvement, annular lesions may occur in other areas [
26]. Central atrophy may be present.
●Bullous lichen planus – Patients with bullous lichen planus develop vesicles or bullae within the sites of existing cutaneous lichen planus lesions. The legs are a common site of lesion development [
2].
●Actinic lichen planus – Actinic lichen planus (also known as lichen planus tropicus) presents with a photodistributed eruption of hyperpigmented macules, annular papules, or plaques [
2]. This variant is most commonly seen in the Middle East, India, and east Africa [
4].
●Lichen planus pigmentosus – Lichen planus pigmentosus presents with gray-brown or dark brown macules or patches that are most commonly found in sun-exposed or flexural areas [
27]. Pruritus is minimal or absent. The term “lichen planus pigmentosus-inversus” is used to describe patients with primarily flexural involvement [
28].
●Inverse lichen planus – Inverse lichen planus is characterized by erythematous to violaceous papules and plaques in intertriginous sites, such as the axillae, inguinal creases, inframammary area, or limb flexures (
picture 8) [
2]. Associated hyperpigmentation is common. Scale and erosions may be present.
●Atrophic lichen planus – Atrophic lichen planus presents with violaceous, round or oval, atrophic plaques. The legs are a common site of involvement [
2], and lesions often clinically resemble extragenital lichen sclerosus. A rare annular atrophic variant of lichen planus characterized by violaceous papules that enlarge peripherally leaving an atrophic center that demonstrates complete loss of elastic fibers on pathology has also been reported [
29-31].
Additional variants include palmoplantar lichen planus (a variant that may demonstrate ulceration) [
32-34] and perforating [
35,36] lichen planus.
Overlap syndromes — Lichen planus pemphigoides and lichen planus-lupus erythematous overlap syndrome are disorders that are characterized by the presence of features of cutaneous lichen planus and a second disease.
●Lichen planus pemphigoides –
Lichen planus pemphigoides presents with overlapping features of lichen planus and bullous pemphigoid. The onset of lichen planus usually precedes the onset of bullous lesions [
37].
Patients develop bullae in sites of previously normal appearing skin and on top of lesions of lichen planus [
37]. This contrasts with bullous lichen planus, which presents with bullae that are limited to longstanding lichen planus lesions. Similar to bullous pemphigoid, direct immunofluorescence studies of lichen planus pemphigoides demonstrate linear deposition of IgG and C3 at the dermal-epidermal junction. (See
"Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Direct immunofluorescence'.)
●Lichen planus-lupus erythematosus overlap syndrome –
The term lichen planus-lupus erythematous overlap syndrome refers to a rare condition in which patients develop skin lesions with clinical, histologic,
and/orimmunopathologic features of both diseases. Clinically, patients often present with blue-red atrophic plaques or upper extremity verrucous papules or nodules [
38].
Other forms of lichen planus — Other manifestations of lichen planus may be present in patients with cutaneous lesions.
●Lichen planopilaris –
Lichen planopilaris is the term used to describe lichen planus that occurs on the scalp. Patients present with areas of hair loss with keratotic follicular papules that, left untreated, can progress to scarring alopecia (
picture 10). Hair regrowth does not occur once follicles are destroyed. (See
"Lichen planopilaris".)
●Genital lichen planus –
Genital lichen planus in men presents with violaceous papules on the glans penis (
picture 7B, 7D), while in women lesions typically occur on the vulva. The vulvo-vaginal-gingival syndrome is an erosive form of lichen planus that involves the epithelium of the vulva, vestibule, vagina, and mouth; it is particularly resistant to treatment [
39,40]. Although all three areas can be affected, the lesions may not be concurrent. The gingival epithelium is usually involved, but erosions, white plaques, or a whitish and lace-like reticular pattern may occur on the buccal mucosa, tongue, and palate (
picture 12). (See
"Vulvar lichen planus".)
●Esophageal lichen planus –
Lichen planus may involve the esophagus, presenting with or without symptoms such as dysphagia or odynophagia [
41]. Possible endoscopic findings include pseudomembranes, friable and inflamed mucosa, submucosal papules, lacy white plaques, erosions, strictures, and other abnormalities (
picture 13). Concomitant oral, genital, or cutaneous lichen planus is frequently present [
41]. The prevalence of esophageal lichen planus is unknown.
●Otic lichen planus – The stratified squamous epithelia of the external auditory canals and tympanic membranes are potential sites for lichen planus. Common clinical features of otic lichen planus include erythema, induration, and stenosis of the external auditory canal; thickening of the tympanic membranes; otorrhea; and hearing loss [
42]. Lichen planus of other body sites may or may not be present. Further study is necessary to determine the prevalence of this disease manifestation.
HISTOPATHOLOGY — Lichen planus is associated with a set of characteristic pathologic findings that are seen in cutaneous lichen planus and to a variable extent in lichen planus of other body sites. These include (
picture 14A-B) [
43,44]:
●Hyperkeratosis without parakeratosis
●Vacuolization of the basal layer
●Civatte bodies (apoptotic keratinocytes) in the lower epidermis
●Wedge-shaped hypergranulosis, “saw-tooth” shaped rete ridges
●Small clefts at the dermal-epidermal junction (Max-Joseph spaces)
●Band-like lymphocytic infiltrate at the dermal-epidermal junction
●Eosinophilic colloid bodies (apoptotic keratinocytes) in the papillary dermis
●Pigment incontinence (most prominent in dark-skinned individuals)
Clinical evaluation — The clinical evaluation of a patient with suspected cutaneous lichen planus consists of a patient interview and a physical examination. Patients should be questioned about medications (drugs that may induce lichen planus (
table 1)), pruritus (a common symptom of cutaneous lichen planus), oral or genital erosions or pain (findings suggestive of concomitant mucosal lichen planus), and dysphagia or odynophagia (findings suggestive of esophageal disease). We also typically inquire about risk factors for hepatitis C. (See
'Screening for HCV' above.)
The physical examination should include an examination of the entire cutaneous surface, including the scalp, as well as examination of the oral cavity and external genitalia. Performing a full examination aids in the assessment of the extent of cutaneous lesions and allows for the recognition of additional sites of involvement.
Immunofluorescence studies are not routinely needed. Direct immunofluorescence may be performed in patients with bullous lesions to differentiate the condition from an autoimmune blistering disease. If performed, direct immunofluorescence often demonstrates colloid bodies in the papillary dermis that stain for complement and immunoglobulins (especially IgM) and irregular fibrin deposition along the dermal-epidermal junction [
43].
Dermoscopy — Wickham’s striae often can be visualized during dermoscopic examination of cutaneous lesions of lichen planus [
45]. (See
"Overview of dermoscopy".)
DIFFERENTIAL DIAGNOSIS — Key disorders in the differential diagnosis for classic presentations of cutaneous lichen planus include the following:
●Lichenoid drug eruption – Lichenoid drug eruptions (drug-induced lichen planus) should always be considered so that the offending agent can be withdrawn when possible (
table 1). The cutaneous manifestations closely resemble idiopathic lichen planus. The patient’s history of drug exposure and a skin biopsy can aid in distinguishing lichenoid drug eruptions from idiopathic lichen planus. Lichenoid drug eruptions usually develop insidiously and can affect any area of the body surface (
picture 15A-D). (See
"Lichenoid drug eruption (drug-induced lichen planus)".)
Other papulosquamous and dermatitic disorders, such as psoriasis, atopic dermatitis, lichen simplex chronicus, subacute cutaneous lupus erythematosus, discoid lupus erythematosus, pityriasis rosea, secondary syphilis, and prurigo nodularis can usually be distinguished from lichen planus through a careful evaluation for clinical findings that are more consistent with these disorders. Lesions suspicious for bullous lichen planus should be distinguished from autoimmune blistering diseases through a biopsy and immunofluorescence studies. Of note, skin involvement in paraneoplastic
pemphigus/paraneoplasticautoimmune multiorgan syndrome (PAMS) often presents as lichenoid skin lesions. (See
"Approach to the patient with cutaneous blisters", section on 'Diagnostic tests' and
"Paraneoplastic pemphigus".)
Comorbid disease — The results of two case-control studies suggest that the prevalence of dyslipidemia may be greater among patients with lichen planus than among individuals without this disease [
47,48]. Additional studies are necessary to confirm an association between dyslipidemia and lichen planus and to explore the clinical relevance of this finding. Further study is also necessary to clarify whether there is an association between oral lichen planus and thyroid disease [
49,50].
TREATMENT — There are few data to support evidence-based recommendations for the treatment of lichen planus [
51-53]. Only a few randomized trials have been performed, most of which were small and subject to methodologic error.
Cutaneous lichen planus — Cutaneous lichen planus usually is a self-limited disorder. Thus, treatment is focused on accelerating resolution and managing pruritus [
1]. (See
'Natural history' above.)
First-line therapy — Topical corticosteroids are commonly used as first-line treatment for localized cutaneous lichen planus. For patients with generalized disease, in whom monotherapy with topical corticosteroids is less practical, topical corticosteroids are often used as an adjunct to systemic therapy or phototherapy. (See
'Second-line therapy' below.)
Topical corticosteroids — Although topical corticosteroids are the mainstay of treatment for patients with localized cutaneous lichen planus, the efficacy of these agents has not been evaluated in clinical studies. Recommendations based upon clinical experience and the relative safety of this mode of treatment support the use of topical corticosteroids as first-line therapy [
1,4].
We typically treat localized cutaneous lichen planus on the trunk and extremities with a high potency or super high potency topical corticosteroid (eg, 0.05%
betamethasone dipropionate, 0.05%
diflorasone diacetate) cream or ointment twice daily (
table 2). Because topical corticosteroid-induced cutaneous atrophy is most likely to occur in intertriginous or facial skin, we prefer to use mid-potency or low-potency corticosteroid creams or ointments when treating these areas. Efficacy should be assessed after two to three weeks.
Intralesional corticosteroids — The thick lesions of hypertrophic lichen planus may be less likely than classic cutaneous lesions to respond well to a topical corticosteroid. Clinical experience suggests that intralesional corticosteroid therapy can be beneficial for the treatment of hypertrophic lichen planus [
4].
We typically administer
triamcinolone acetonide in a concentration of 2.5 to 10
mg/mL. The quantity administered should blanch or at least infiltrate hypertrophic lesions. Extension of the corticosteroid into the surrounding normal skin should be minimized. We limit the total dose of triamcinolone to no more than 40 mg per treatment session. Injections may be repeated after four to six weeks.
Second-line therapy — Patients with cutaneous lichen planus who cannot be treated adequately with local corticosteroids (eg, generalized disease or local corticosteroid-refractory disease) may benefit from other treatments, such as oral glucocorticoids, phototherapy, and oral
acitretin. Only acitretin has been evaluated in a blinded placebo-controlled randomized trial. The limited availability of data and the potential for lichen planus to spontaneously resolve contributes to uncertainty about the efficacy of treatments. The risks and benefits of treatment should be considered carefully prior to treatment.
Systemic glucocorticoids — Oral glucocorticoid therapy may be beneficial for cutaneous lichen planus based upon clinical experience and a few small uncontrolled studies in which improvements in the signs or symptoms of cutaneous lichen planus occurred during oral glucocorticoid therapy [
51,54,55]. We consider prescribing a short course of an oral glucocorticoid when acute control of cutaneous lichen planus is necessary for patients with extensive disease. Continued, long-term treatment with systemic glucocorticoids is less favorable due to the serious side effects associated with long-term therapy. (See
"Major side effects of systemic glucocorticoids".)
The optimal dose and duration of systemic glucocorticoid therapy is not known. Our preference is to begin with 30 to 60 mg daily for four to six weeks followed by a taper of the dose to discontinuation over the next four to six weeks. Lower doses and shorter courses have also been proposed in the literature [
51].
Non-placebo-controlled studies evaluating narrowband UVB for cutaneous lichen planus have generally yielded favorable findings. A small, unblinded, randomized trial of 46 patients with generalized lichen planus that compared treatment with narrowband UVB (three times per week for six weeks) to oral
prednisone (0.3
mg/kg per day for six weeks) found a significantly better response in the patients who received phototherapy [
56]. Complete responses were attained by 12 of 23 patients in the phototherapy group (52 percent) versus 3 of 23 patients in the prednisone group (13 percent).
Several other studies suggest benefit of UVB phototherapy [
57-61]. As an example, a prospective uncontrolled study of 16 patients with generalized cutaneous lichen planus found that 11 patients achieved at least a 90 percent reduction in papules after treatment with narrowband UVB (three times weekly for 40 sessions). Itching tended to improve early in the course of therapy. Additionally, a retrospective study in which 50 patients with generalized cutaneous lichen planus were treated with either narrowband UVB (n = 43) or broadband UVB (n = 7) three times per week found documentation of complete remissions in 70 percent of patients [
58]. Among those who achieved a complete remission, 85 percent remained in remission after a median follow-up period of 34.7 months.
PUVA photochemotherapy, which requires oral or bath administration of 8-methoxypsoralen, also seems to be efficacious for some patients with cutaneous lichen planus based upon retrospective studies and case series [
62-67]. Although the findings of a retrospective analysis of 28 patients with generalized lichen planus raised the question of whether PUVA is more likely than narrowband UVB to induce an initial response [
62], the study failed to find a significant difference in the long term benefit of these treatments. Additional studies are needed to explore the comparative efficacy of PUVA and narrowband UVB phototherapy.
Given the lack of data confirming superiority of a particular mode of phototherapy, narrowband UVB therapy (initially given three times per week) is our preferred mode of phototherapy for cutaneous lichen planus due to the ease with which this treatment can be administered. In contrast to narrowband UVB, PUVA requires administration of an oral or topical photosensitizer. Additionally, oral PUVA requires a period of ocular photoprotection following treatment. We taper the frequency of narrowband UVB treatment once an adequate response is achieved. If no response is observed after three to four months, we discontinue treatment.
Oral retinoids — The best support for the use of
acitretin, an oral retinoid, for lichen planus stems from a placebo-controlled randomized trial of 65 patients with cutaneous lichen planus [
68]. At the end of eight weeks, patients treated with 30 mg per day of acitretin (n = 32) were significantly more likely to have achieved remission or marked improvement than the 33 patients in the placebo group (64 versus 13 percent achieved this level of response). Improvement during treatment with acitretin and other oral retinoids has also been documented in small, open-label studies or case reports [
69-71].
Although the randomized trial strongly supports a beneficial effect of
acitretin on cutaneous lichen planus, the potential adverse effects of acitretin account for our categorization of acitretin as a second-line treatment rather than a first-line treatment for cutaneous lichen planus. Xerosis, hair loss, hypertriglyceridemia, visual changes, myalgias, pseudotumor cerebri, and skeletal abnormalities are some examples of retinoid side effects. We primarily reserve the use of acitretin for patients with disease that cannot be managed with local corticosteroids or phototherapy.
Oral retinoids should be administered by or in consultation with clinicians familiar with the use and side effects of this therapy (eg, a dermatologist).
Acitretin is teratogenic, and is contraindicated for women who are pregnant or intend to become pregnant. Pregnancy is contraindicated for three years after discontinuation of acitretin.
Other treatments — Oral antihistamines (eg,
hydroxyzine hydrochloride 10 to 50 mg four times a day, as necessary) may be helpful in controlling pruritus. Other medications that have been reported to be of benefit in some patients with cutaneous lichen planus include
thalidomide [
72,73], low molecular weight heparin [
74,75],
griseofulvin [
76],
cyclosporine [
51],
dapsone[
3,77],
sulfasalazine [
78],
metronidazole [
79,80], and
hydroxychloroquine [
81].
Mycophenolate mofetil has been used successfully in the treatment of at least two patients with extensive generalized lichen planus and one patient with resistant hypertrophic and bullous lichen planus [
82,83]. Further study is necessary to confirm the efficacy of all of these agents.
The results of a small uncontrolled study suggest that
apremilast, a phosphodiesterase inhibitor that is not yet available for clinical use, may be beneficial for lichen planus [
84]. Treatment with apremilast (20 mg twice daily for 12 weeks) was associated with clinical improvement in all 10 patients, including three patients who achieved at least a two-grade improvement in the physician global assessment score. Additional studies are necessary to explore the efficacy and safety of apremilast for lichen planus.
Other types of lichen planus
Genital lichen planus — Topical corticosteroids or topical calcineurin inhibitors are often used in the treatment of genital lichen planus. The treatment of vulvar lichen planus is reviewed in detail elsewhere. (See
"Vulvar lichen planus".)
Lichen planopilaris — The treatment of lichen planopilaris (LPP) can be difficult. Topical corticosteroids or intralesional corticosteroids are often used as first-line therapies (
table 2) [
85-88]. The treatment of LPP is discussed in greater detail separately. (See
"Lichen planopilaris", section on 'Treatment'.)
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SUMMARY AND RECOMMENDATIONS
●Lichen planus is a mucocutaneous disorder that most commonly affects middle-aged adults. Clinicians should be aware of the potential for drug-induced forms of lichen planus. (See
'Introduction' above and
'Etiology' above.)
●Studies have suggested an association of lichen planus with hepatitis C virus (HCV), although the strength of this association varies geographically. Further studies are necessary to determine if HCV screening should be performed in patients with lichen planus. (See
'Hepatitis C virus' above.)
●Lichen planus may affect the skin, nails, or mucous membranes. Cutaneous lichen planus typically presents as pruritic, polygonal, violaceous papules
and/or plaques with an overlying white, lacelike pattern (Wickham's striae) (
picture 1A-D). Significant post-inflammatory hyperpigmentation is common. Cutaneous lichen planus may also present with hypertrophic or vesicobullous lesions. (See
'Clinical features' above.)
●Cutaneous lichen planus often spontaneously resolves after one to two years. Oral, genital, scalp, and nail lichen planus tend to be more chronic. (See
'Natural history' above.)
●We suggest high potency or super high potency topical corticosteroids as initial treatment of localized cutaneous lichen planus on the trunk or extremities based upon clinical experience and the relative safety of this therapy (
Grade 2C). Intralesional corticosteroids can be useful in patients with hypertrophic lichen planus. Patients with widespread cutaneous disease may benefit from phototherapy,
acitretin, or a short course of systemic glucocorticoid therapy. (See
'Treatment' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate, Inc. would like to acknowledge Dr. Fuad Muakkassa for his contributions to this topic review.
(National Heart, Lung, and Blood Institute)
