Lichen Planus

Practice Essentials

Lichen planus is a cell-mediated immune response of unknown origin. It may be found with other diseases of altered immunity, such as ulcerative colitis, alopecia areata, vitiligo, dermatomyositis, morphea, lichen sclerosis, and myasthenia gravis. Lichen planus (see the image below) has been found to be associated with hepatitis C virus infection.^{[1, 2, 3, 4, 5]}

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Close-up view of lichen planus.

Signs and symptoms

The following may be noted in the patient history:

• Lesions initially developing on flexural surfaces of the limbs, with a generalized eruption developing after a week or more and maximal spreading within 2-16 weeks
• Pruritus of varying severity, depending on the type of lesion and the extent of involvement
• Oral lesions that may be asymptomatic, burning, or even painful
• In cutaneous disease, lesions typically resolve within 6 months (>50%) to 18 months (85%); chronic disease is more likely oral lichen planus or with large, annular, hypertrophic lesions and mucous membrane involvement

In addition to the widespread cutaneous eruption, lichen planus can involve the following structures:

• Mucous membranes
• Genitalia
• Nails
• Scalp

The clinical presentation of lichen planus has several variations, as follows:

• Hypertrophic lichen planus
• Atrophic lichen planus
• Erosive/ulcerative lichen planus
• Follicular lichen planus (lichen planopilaris)
• Annular lichen planus
• Linear lichen planus
• Vesicular and bullous lichen planus
• Actinic lichen planus
• Lichen planus pigmentosus
• Lichen planus pemphigoides

See Clinical Presentation for more detail.

Diagnosis

Direct immunofluorescence study reveals globular deposits of immunoglobulin M (IgM) and complement mixed with apoptotic keratinocytes. No imaging studies are necessary.

Distinguishing histopathologic features of lichen planus include the following:

• Hyperkeratotic epidermis with irregular acanthosis and focal thickening in the granular layer
• Degenerative keratinocytes (colloid or Civatte bodies) in the lower epidermis; in addition to apoptotic keratinocytes, colloid bodies are composed of globular deposits of IgM (occasionally immunoglobulin G [IgG] or immunoglobulin A [IgA]) and complement
• Linear or shaggy deposits of fibrin and fibrinogen in the basement membrane zone
• In the upper dermis, a bandlike infiltrate of lymphocytic (primarily helper T) and histiocytic cells with many Langerhans cells

See Workup for more detail.

Management

Lichen planus is a self-limited disease that usually resolves within 8-12 months. Mild cases can be treated with fluorinated topical steroids. More severe cases, especially those with scalp, nail, and mucous membrane involvement, may necessitate more intensive therapy.

Pharmacologic therapies include the following:

• Cutaneous lichen planus: Topical steroids, particularly class I or II ointments (first-line treatment); systemic steroids; oral regimens like metronidazole, acitretin, methotrexate, hydroxychloroquine, griseofulvin, and sulfasalazine^{[6, 7, 8, 9]} ; and other treatments with unproven efficacy (eg, mycophenolate mofetil)
• Lichen planus of the oral mucosa: Topical steroids; topical calcineurin inhibitors; oral or topical retinoids (with close monitoring of lipid levels^[10] )

Patients with widespread lichen planus may respond to the following:

• Narrow-band or broadband UV-B radiation^{[11, 6, 7]}
• Psoralen with UV-A (PUVA) radiation;^{[6, 7]} use of topical ointment at the time of UV-A treatment may decrease the effectiveness of PUVA; precautions should be taken for persons with a history of skin cancers or hepatic insufficiency

See Treatment and Medication for more detail.

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Background

Lichen planus (LP) is a pruritic eruption commonly associated with hepatitis C. Lesions are characteristically papular, purple (violaceous color), polygonal, and peripherally located (eg. on the distal extremities). LP may also affect the genitalia or mucous membranes. It is most likely an immunologically mediated reaction, though the pathophysiology in unclear. See Oral Lichen Planus for more information on this variant of lichen planus.

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Pathophysiology

Lichen planus is a cell-mediated immune response of unknown origin. It may be found with other diseases of altered immunity; these conditions include ulcerative colitis, alopecia areata, vitiligo, dermatomyositis, morphea, lichen sclerosis, and myasthenia gravis.

An association is noted between lichen planus and hepatitis C virus infection,^{[2, 3, 4, 5]} chronic active hepatitis, and primary biliary cirrhosis.^[12] In one meta-analysis, 16% of patients with LP had hepatitis C infection.^[3] This association has been shown to exist in all regions of the world, including North America.^[4] A workup for hepatitis C should be considered in patients with widespread or unusual presentations of lichen planus. Onset or exacerbation of lichen planus has also been linked to stressful events.^[13]

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Etiology

The exact cause of lichen planus is not known, although it is immunologically mediated. The initiating antigen is unclear; however, Langerhans cells process the antigen to T lymphocytes, resulting in an epidermotropic infiltrate. Histologically, the inflammation is described as a lichenoid infiltrated, effacing the dermo-epidermal junction.

Some patients with lichen planus have a positive family history. It has been noted that affected families have an increased frequency of human leukocyte antigen B7 (HLA-B7). Others have found an association between idiopathic lichen planus and human leukocyte antigen DR1 (HLA-DR1) and human leukocyte antigen DR10 (HLA-DR10); thus, lichen planus may be influenced by a genetic predisposition.

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Epidemiology

Frequency

United States

Lichen planus is reported in approximately 1% of all new patients seen at health care clinics. Some areas have reported a higher incidence in December and January.

International

No significant geographical variation in frequency exists for lichen planus.

Race

No racial predispositions have been noted for lichen planus.

Sex

No significant differences in incidence for lichen planus are noted between male and female patients, but in women, lichen planus may present as desquamative inflammatory vaginitis.^[14]

Age

More than two thirds of lichen planus patients are aged 30-60 years; however, lichen planus can occur at any age.^[15]

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Prognosis

The prognosis for lichen planus is good, as most cases regress within 18 months. Some cases recur. In lichen planus, atrophy and scarring are seen in hypertrophic lesions and in lesions on the scalp. Cutaneous lichen planus does not carry a risk of skin cancer, but ulcerative lesions in the mouth, particularly in men, do have a low rate of malignant transformation. However, the malignant transformation rate of oral lichen planus is low (< 2% in one report).^[16] Vulvar lesions in women may also be associated with squamous cell carcinoma.

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Patient Education

Patients should be told about the self-limiting nature of lichen planus. Because lichen planus is not common, no large, randomized, controlled clinical trials have been conducted for therapy. Several treatments may need to be tried.

Patients should be told about the small likelihood of recurrence and the potential adverse effects from the various treatments offered.

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History

Most cases of lichen planus (LP) are insidious. Lesions usually develop on flexural surfaces of the limbs, such as the wrists (see the image below). After a week or more, a generalized eruption develops with maximal spreading within 2-16 weeks.

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Lichen planus on the flexor part of the wrist.

Pruritus is common in lichen planus but varies in severity depending on the type of lesion and the extent of involvement. Hypertrophic lesions are extremely pruritic.

Oral lesions may be asymptomatic or have a burning sensation, or they may even be painful if erosions are present.

In more than 50% of patients with cutaneous disease, the lesions resolve within 6 months, and 85% of cases subside within 18 months. On the other hand, oral lichen planus had been reported to have a mean duration of 5 years. Large, annular, hypertrophic lesions and mucous membrane involvement are more likely to become chronic.

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Physical Examination

In addition to the cutaneous eruption, lichen planus (LP) can involve the mucous membranes, the genitalia, the nails, and the scalp. The clinical presentation of lichen planus has several forms: actinic (in sun-exposed areas), annular, atrophic, erosive, follicular, hypertrophic, linear, pigmented, and vesicular/bullous. The papules are violaceous, shiny, and polygonal; varying in size from 1 mm to greater than 1 cm in diameter (see the image below). They can be discrete or arranged in groups of lines or circles. Characteristic fine, white lines, called Wickham stria, are often found on the papules (see the image below).

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Close-up view of lichen planus.

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Lichen planus shows Wickham striae (white, fine, reticular scales).

Mucous membrane involvement is common and may be found in patients who do not have skin involvement. Lesions are most commonly found on the tongue and the buccal mucosa; they are characterized by white or gray streaks forming a linear or reticular pattern on a violaceous background (see the image below). Oral lesions are classified as reticular, plaquelike, atrophic, papular, erosive, and bullous. Ulcerated oral lesions may have a higher incidence of malignant transformation in men, but this observation may be confounded by other factors, such as smoking and chewing tobacco. Lesions may also be found on the conjunctivae, the larynx, the esophagus, the tonsils, the tympanic membrane, the bladder, the vulva, and the vaginal vault; throughout the gastrointestinal tract; and around the anus.

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Lichen planus on the oral mucosa with ulceration in the center of the lesion appears with whitish papules and plaques in the periphery.

Genital involvement is common in lichen planus. Typically, men develop annular lesions on the glans. Wickham striae may also be observed on these lesions. Vulvar involvement can range from reticulate papules to severe erosions. Dyspareunia, a burning sensation, and pruritus are common in women. Vulvar and urethral stenosis may be a complication. It is estimated that more than 50% of women with oral lichen planus also had undiagnosed vulvar lichen planus.^{[17, 18]}

Nail findings are found in roughly 10% of patients with lichen planus. Thes findings are most commonly longitudinal grooving and ridging. Hyperpigmentation, subungual hyperkeratosis, onycholysis, and longitudinal melanonychia can result from lichen planus. Rarely, inflammation may result in permanent destruction of the nail matrix with subsequent pterygium formation. Lichen planus has been linked to childhood idiopathic nail atrophy and may overlap with twenty-nail dystrophy of childhood.

Cutaneous lesions may be accompanied by follicular and perifollicular lesions on the scalp, which may be violaceous, scaly, and pruritic papules. These lesions can progress to atrophic cicatricial alopecia, known as lichen planopilaris. This can appear even many weeks after the skin lesions have disappeared. Pseudopelade can be a final endpoint.

Variations in lichen planus include the following:

• Hypertrophic lichen planus: These extremely pruritic lesions are most often found on the extensor surfaces of the lower extremities, especially around the ankles. Hypertrophic lesions are often chronic; residual pigmentation and scarring can occur when the lesions eventually clear.
• Atrophic lichen planus: Atrophic lichen planus is characterized by a few lesions, which are often the resolution of annular or hypertrophic lesions.
• Erosive/ulcerative lichen planus: These lesions are found on the mucosal surfaces and evolve from sites of previous lichen planus involvement. A rare variant of lichen planus is vulvovaginal-gingival syndrome.^[19] It is characterized by erosions and desquamation of the mucosa in the vulval, vaginal, and gingival regions. It can be associated with mucocutaneous scarring and vaginal stricture formation.
• Follicular lichen planus (also known as lichen planopilaris): This is characterized by keratotic papules that may coalesce into plaques. This condition is more common in women than in men, and ungual and erosive mucosal involvement is more likely to be present. A scarring alopecia may result. A variant of lichen planopilaris is frontal fibrosing alopecia. It is characterized by marginal progressive hair loss on the scalp, eyebrows, and axillae.^[20] Another variant of follicular lichen planus is Graham-Little-Piccardi-Lasseur syndrome.^[21] Features of this syndrome include progressive scalp cicatricial alopecia, noncicatricial alopecia of the axillae and pubic areas, and keratosis pilaris–like follicular papules over the trunk and extremities.
• Annular lichen planus: Lichen planus papules that are purely annular are rare. Annular lesions with an atrophic center can be found on the buccal mucosa and the male genitalia.
• Linear lichen planus: Isolated linear lesions may form a zosteriform lesion, or they may develop as a Köebner effect.
• Vesicular and bullous lichen planus: Most commonly, these lesions develop on the lower limbs or in the mouth from preexisting lichen planus lesions. A rare condition, lichen planus pemphigoides, is a combination of both lichen planus and bullous pemphigoid.
• Actinic lichen planus: Subtropic or actinic lichen planus occurs in regions, such as Africa, the Middle East, and India. This mildly pruritic eruption usually spares the nails, the scalp, the mucous membranes, and covered areas. Lesions are characterized by nummular patches with a hypopigmented zone surrounding a hyperpigmented center.
• Lichen planus pigmentosus: This is a rare variant of lichen planus but can be more common in persons with darker-pigmented skin, such as Latinos or Asians. It usually appears on face and neck. Some believe it is similar to or the same as erythema dyschromicum perstans (ie, ashy dermatosis).
• Lichen planus pemphigoides: This is a rare form of lichen planus. Blisters subsequently develop on lichen planus lesions. Clinically, histopathologically and immunopathologically, it has features of lichen planus and bullous pemphigoid, it but carries a better prognosis than pemphigoid.

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Complications

Malignant transformation has been reported in ulcerative oral lichen planus (OLP).^[22] Cutaneous hypertrophic lichen planus resulting in squamous cell carcinoma (SCC) was reported in a series of 38 patients.^[23] Pruritic and painful vulvar lichen planus has been a precursor to SCC in a small number of cases.

Infection, osteoporosis, adrenal insufficiency, bone marrow suppression, renal damage, hyperlipidemia, and growth restriction in children may occur due to medication adverse effects. Postinflammatory/residual hyperpigmentation may be a common marker after lichen planus has subsided. Alopecia associated with lichen planus is often permanent.

Hepatitis C virus infection may be present in 16% of lichen planus patients. Additionally, a meta-analysis reported that hepatitis C virus seropositivity could be 6 times higher in oral lichen planus patients than controls.^[1]

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Laboratory Studies

Direct immunofluorescence study in lichen planus (LP) reveals globular deposits of immunoglobulin M (IgM) and complement mixed with apoptotic keratinocytes.

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Imaging Studies

No imaging studies are necessary for lichen planus.

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Histologic Findings

The histopathologic features distinguish lichen planus based on the presence of irregular acanthosis and colloid bodies in the epidermis with destruction of the basal layer. The upper dermis has a bandlike ("lichenoid") infiltrate of lymphocytes and histiocytes.

The inflammatory reaction pattern is characteristic. The epidermis is hyperkeratotic with irregular acanthosis and focal thickening in the granular layer. Degenerative keratinocytes, known as colloid or Civatte bodies, are found in the lower epidermis. In addition to apoptotic keratinocytes, colloid bodies are composed of globular deposits of IgM (occasionally immunoglobulin G [IgG] or immunoglobulin A [IgA]) and complement. Linear or shaggy deposits of fibrin and fibrinogen are noted in the basement membrane zone.

The upper dermis has a bandlike infiltrate of lymphocytic (primarily helper T) and histiocytic cells with many Langerhans cells. The infiltrate is very close to the epidermis and often disrupts the dermal-epidermal junction.

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Medical Care

Lichen planus (LP) is a self-limited disease that usually resolves within 8-12 months. Mild cases can be treated with fluorinated topical steroids. More severe cases, especially those with scalp, nail, and mucous membrane involvement, may need more intensive therapy.

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Consultations

Consult a dermatologist.

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Medication Summary

The first-line treatments of cutaneous lichen planus are topical steroids, particularly class I or II ointments. A second choice would be systemic steroids for symptom control and possibly more rapid resolution. Many practitioners prefer intramuscular triamcinolone 40-80 mg every 6-8 weeks. Oral metronidazole has been shown to be an effective therapy for some patients.^[8] Oral acitretin has been shown to be effective in published studies.^[24] Many other treatments, including mycophenolate mofetil at 1-1.5 g twice daily, are of uncertain efficacy, owing to the paucity of experience. In a randomized double-blinded study, sulfasalazine at up to 2.5 g/day for 6 weeks showed improvement in lesions (>80%) and pruritus (>90%) in patients with generalized lichen planus.^[9]

For lichen planus of the oral mucosa, topical steroids are usually tried first. Topical and systemic cyclosporin have been tried with some success^[25] ; however, a randomized double-blind study indicated that topical cyclosporin was a less effective but much more costly regimen than clobetasol.^[26] Newer topical calcineurin inhibitors have replaced topical cyclosporin for the treatment of lichen planus. Other options include oral or topical retinoids. Even with these effective treatments, relapses are common.

Close monitoring of lipid levels is suggested for patients with lichen planus who are treated with oral retinoid agents because a case control study found that the risk of dyslipidemia in these patients is increased 2-3 fold.^[10]   In fact, according to a meta-analysis of 5,242 patients, even those who did not receive retinoids might still have dyslipidemia.

Patients with widespread lichen planus may respond to narrow-band or broadband UV-B therapy.^[11] Psoralen with UV-A (PUVA) therapy for 8 weeks has been reported to be effective. Risks and benefits of this treatment should be considered. PUVA is carcinogenic. Long-term risks include dose-related actinic degeneration, squamous cell carcinoma, and cataracts. A phototoxic reaction with erythema, pruritus, phytophotodermatitis, and friction blisters could occur.

UV-A therapy combined with oral psoralen consists of oral psoralen (0.6 mg/kg), 1.5-2 hours before ultraviolet light, which usually starts at 0.5-1 J/cm² and is increased by 0.5 J/cm² per visit. Use of topical ointment at the time of receiving UV-A treatment may decrease the effectiveness of PUVA. Precaution should be taken for persons with a history of skin cancers or hepatic insufficiency.

Apremilast may be an effective treatment for lichen planus but double-blinded, controlled trials are lacking.^[27]

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Prednisone

• Dosing, Interactions, etc.

Clinical Context:  Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Use with extreme caution in children. The pediatric dose is determined more by severity of the condition than by age or weight.

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Betamethasone topical (Diprolene, Celestone, Luxiq)

• Dosing, Interactions, etc.

Clinical Context:  Betamethasone is for inflammatory dermatosis responsive to steroids. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. Use with extreme caution in pediatric patients. Children have a larger skin surface area to body weight ratio and less developed, thinner skin, which may result in greater amounts of topical steroid being absorbed compared with adults. Use nonfluorinated topical corticosteroids.

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Triamcinolone (Aristospan, Kenalog)

• Dosing, Interactions, etc.

Clinical Context:  Triamcinolone is for inflammatory dermatoses responsive to steroids. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. Local injections have been reported to be effective.

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Halobetasol (Ultravate, Halonate)

• Dosing, Interactions, etc.

Clinical Context:  Halobetasol is used for inflammatory dermatoses responsive to steroids. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. Use with extreme caution in pediatric patients. Children have a larger ratio of skin surface area to body weight and less developed, thinner skin, which may result in greater amounts of topical steroid being absorbed compared with adults. Use nonfluorinated topical corticosteroids.

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Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli. Topical steroids may be as effective as systemic steroids. Class I or II steroids in ointment form reduce pruritus in cutaneous lichen planus, but they have not been proven to induce remission.

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Isotretinoin (Amnesteem, Claravis, Myorisan, Sotret)

• Dosing, Interactions, etc.

Clinical Context:  Isotretinoin is an oral agent that treats serious dermatologic conditions. It is a synthetic 13-cis isomer of the naturally occurring tretinoin (trans- retinoic acid). Both agents are structurally related to vitamin A. Isotretinoin decreases sebaceous gland size and sebum production. It may inhibit sebaceous gland differentiation and abnormal keratinization.

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Tretinoin topical (Retin-A, Avita, Renova, Atralin, Tretin-X)

• Dosing, Interactions, etc.

Clinical Context:  Tretinoin may be effective for oral lichen planus but not for cutaneous disease. It inhibits microcomedo formation and eliminates existing lesions. Tretinoin makes keratinocytes in sebaceous follicles less adherent and easier to remove. It is available as 0.025%, 0.05%, and 0.1% creams and 0.01% and 0.025% gels.

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Acitretin (Soriatane)

• Dosing, Interactions, etc.

Clinical Context:  Acitretin is a retinoic acid analog, like etretinate and isotretinoin. Etretinate is the main metabolite and has demonstrated clinical effects close to those seen with etretinate. Its mechanism of action is unknown.

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Class Summary

These agents modulate cell proliferation.

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Cyclosporine (Sandimmune, Neoral, Gengraf)

• Dosing, Interactions, etc.

Clinical Context:  Topical treatment with cyclosporine under occlusion has been efficacious for genital lesions and may be beneficial in hypertrophic lesions. Mouthwash or oil-based solutions have been effective for oral lichen planus but seem to be no better than corticosteroids. Systemic treatment has been used for severe resistant cutaneous disease, oral or ulcerative foot involvement, and lichen planopilaris of the scalp.

The pediatric population may require higher or more frequent dosing because of accelerated clearance; use with extreme caution.

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Class Summary

These agents modulate the immune system.

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Metronidazole (Flagyl)

• Dosing, Interactions, etc.

Clinical Context:  Oral metronidazole is an imidazole ring-based antibiotic that has been shown to be an effective therapy for some patients presenting with lichen planus. Its mechanism is unknown.

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Class Summary

These drugs may have antibacterial and/or anti-inflammatory effects that are responsible for their effectiveness in the treatment of cutaneous lichen planus.

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