Lichen Planus

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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 has been found to be associated with hepatitis C virus infection,[1, 2, 3, 4] chronic active hepatitis, and primary biliary cirrhosis.[5]

Essential update: New study of apremilast for severe lichen planus

Paul et al examined the safety and efficacy of apremilast for the treatment of moderate to severe chronic lichen planus in an open-label pilot study of 10 patients with biopsy-proven disease.[6] After 12 weeks of treatment, 3 of the 10 patients achieved a 2-grade or more improvement in the Physician Global Assessment, and all showed significant clinical improvement in secondary parameters. Larger controlled studies will be needed to establish the long-term safety and efficacy of apremilast therapy for lichen planus.

Signs and symptoms

The following may be noted in the patient history:

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

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

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:

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:

Patients with widespread lichen planus may respond to the following:

See Treatment and Medication for more detail.

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

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.

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,[1, 2, 3, 4] chronic active hepatitis, and primary biliary cirrhosis.[5] In one meta-analysis, 16% of patients with LP had hepatitis C infection.[2] This association has been shown to exist in all regions of the world, including North America.[3] 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.[11]

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.

Mortality/Morbidity

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 higher incidence of malignant transformation. However, the malignant transformation rate of oral lichen planus is low (< 2% in one report).[12] Vulvar lesions in women may also be associated with squamous cell carcinoma.

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.[13]

Age

More than two thirds of lichen planus patients are aged 30-60 years; however, lichen planus can occur at any age.[14]

History

Most cases of lichen planus (LP) are insidious.

Physical

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 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.[15, 16] (Also see the clinical guideline summary, Diagnosis and management of vulvar skin disorders.[17] )

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:

Causes

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.

Laboratory Studies

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

Imaging Studies

No imaging studies are necessary for lichen planus.

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.

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.

Consultations

Consult a dermatologist.

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.[7] Oral acitretin has been shown to be effective in published studies.[18] Many other treatments, including mycophenolate mofetil at 1-1.5 g twice daily, are of uncertain efficacy because of the lack of randomized controlled trials. 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.[8]

For lichen planus of the oral mucosa, topical steroids are usually tried first. Topical and systemic cyclosporin have been tried with some success[19] ; however, a randomized double-blind study indicated that topical cyclosporin was a less effective but much more costly regimen than clobetasol.[20] 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.[9]

Patients with widespread lichen planus may respond to narrow-band or broadband UV-B therapy.[10] 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.

Prednisone

Clinical Context:  May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Use with extreme caution in children. Pediatric dose is determined more by severity of condition than by age or weight.

Betamethasone topical (Diprolene, Celestone, Luxiq)

Clinical Context:  For inflammatory dermatosis responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Use in pediatrics with extreme caution. 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.

Triamcinolone (Aristospan, Kenalog)

Clinical Context:  For inflammatory dermatosis responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Local injections have been reported to be effective.

Halobetasol (Ultravate, Halonate)

Clinical Context:  For inflammatory dermatosis responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Use in pediatrics with extreme caution. 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.

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.

Isotretinoin (Amnesteem, Claravis, Myorisan, Sotret)

Clinical Context:  Oral agent that treats serious dermatologic conditions. Synthetic 13-cis isomer of the naturally occurring tretinoin (trans- retinoic acid). Both agents are structurally related to vitamin A. Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization.

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

Clinical Context:  May be effective for oral LP but not for cutaneous disease. Inhibits microcomedo formation and eliminates existing lesions. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025%, 0.05%, and 0.1% creams. Also available as 0.01% and 0.025% gels.

Acitretin (Soriatane)

Clinical Context:  Retinoic acid analog, like etretinate and isotretinoin. Etretinate is main metabolite and has demonstrated clinical effects close to those seen with etretinate. Mechanism of action is unknown.

Class Summary

These agents modulate cell proliferation.

Cyclosporine (Sandimmune, Neoral, Gengraf)

Clinical Context:  Topical treatment 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 LP 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.

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

Class Summary

These agents modulate the immune system.

Metronidazole (Flagyl)

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. Mechanism is unknown.

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.

Complications

Prognosis

Author

Tsu-Yi Chuang, MD, MPH, Clinical Professor, Department of Dermatology, Keck School of Medicine of the University of Southern California; Staff Dermatologist, Desert Oasis Healthcare

Disclosure: Nothing to disclose.

Coauthor(s)

Laura Stitle, MD, Staff Physician, Department of Dermatology, Indiana University Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Joshua A Zeichner, MD, Assistant Professor, Director of Cosmetic and Clinical Research, Mount Sinai School of Medicine; Chief of Dermatology, Institute for Family Health at North General

Disclosure: Valeant Consulting fee Consulting; Medicis Grant/research funds Other; Galderma Consulting fee Consulting; Promius Consulting fee Consulting; Pharmaderm Consulting fee Consulting; Onset Consulting fee Consulting

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD, Director, Ackerman Academy of Dermatopathology, New York

Disclosure: Nothing to disclose.

References

  1. Chuang TY, Stitle L, Brashear R, Lewis C. Hepatitis C virus and lichen planus: A case-control study of 340 patients. J Am Acad Dermatol. Nov 1999;41(5 Pt 1):787-9. [View Abstract]
  2. [Best Evidence] Shengyuan L, Songpo Y, Wen W, Wenjing T, Haitao Z, Binyou W. Hepatitis C virus and lichen planus: a reciprocal association determined by a meta-analysis. Arch Dermatol. Sep 2009;145(9):1040-7. [View Abstract]
  3. Bigby M. The relationship between lichen planus and hepatitis C clarified. Arch Dermatol. Sep 2009;145(9):1048-50. [View Abstract]
  4. Raslan HM, Ezzat WM, Abd El Hamid MF, Emam H, Amre KS. Skin manifestations of chronic hepatitis C virus infection in Cairo, Egypt. East Mediterr Health J. May-Jun 2009;15(3):692-700. [View Abstract]
  5. Korkij W, Chuang TY, Soltani K. Liver abnormalities in patients with lichen planus. A retrospective case-control study. J Am Acad Dermatol. Oct 1984;11(4 Pt 1):609-15. [View Abstract]
  6. Paul J, Foss CE, Hirano SA, Cunningham TD, Pariser DM. An open-label pilot study of apremilast for the treatment of moderate to severe lichen planus: A case series. J Am Acad Dermatol. Feb 2013;68(2):255-61. [View Abstract]
  7. Rasi A, Behzadi AH, Davoudi S, Rafizadeh P, Honarbakhsh Y, Mehran M, et al. Efficacy of oral metronidazole in treatment of cutaneous and mucosal lichen planus. J Drugs Dermatol. Oct 2010;9(10):1186-90. [View Abstract]
  8. [Best Evidence] Omidian M, Ayoobi A, Mapar M, Feily A, Cheraghian B. Efficacy of sulfasalazine in the treatment of generalized lichen planus: randomized double-blinded clinical trial on 52 patients. J Eur Acad Dermatol Venereol. Feb 10 2010;[View Abstract]
  9. Arias-Santiago S, Buendia-Eisman A, Aneiros-Fernandez J, et al. Cardiovascular risk factors in patients with lichen planus. Am J Med. Jun 2011;124(6):543-8. [View Abstract]
  10. Pavlotsky F, Nathansohn N, Kriger G, Shpiro D, Trau H. Ultraviolet-B treatment for cutaneous lichen planus: our experience with 50 patients. Photodermatol Photoimmunol Photomed. Apr 2008;24(2):83-6. [View Abstract]
  11. Manolache L, Seceleanu-Petrescu D, Benea V. Lichen planus patients and stressful events. J Eur Acad Dermatol Venereol. Apr 2008;22(4):437-41. [View Abstract]
  12. Ingafou M, Leao JC, Porter SR, Scully C. Oral lichen planus: a retrospective study of 690 British patients. Oral Dis. Sep 2006;12(5):463-8. [View Abstract]
  13. Murphy R, Edwards L. Desquamative inflammatory vaginitis: what is it?. J Reprod Med. Feb 2008;53(2):124-8. [View Abstract]
  14. Balasubramaniam P, Ogboli M, Moss C. Lichen planus in children: review of 26 cases. Clin Exp Dermatol. Jul 2008;33(4):457-9. [View Abstract]
  15. Belfiore P, Di Fede O, Cabibi D, et al. Prevalence of vulval lichen planus in a cohort of women with oral lichen planus: an interdisciplinary study. Br J Dermatol. Nov 2006;155(5):994-8. [View Abstract]
  16. Di Fede O, Belfiore P, Cabibi D, et al. Unexpectedly high frequency of genital involvement in women with clinical and histological features of oral lichen planus. Acta Derm Venereol. 2006;86(5):433-8. [View Abstract]
  17. [Guideline] American College of Obstetricians and Gynecologists. Diagnosis and management of vulvar skin disorders. National Guideline Clearinghouse. May 2008.
  18. Cribier B, Frances C, Chosidow O. Treatment of lichen planus. An evidence-based medicine analysis of efficacy. Arch Dermatol. Dec 1998;134(12):1521-30. [View Abstract]
  19. Lim KK, Su WP, Schroeter AL, Sabers CJ, Abraham RT, Pittelkow MR. Cyclosporine in the treatment of dermatologic disease: an update. Mayo Clin Proc. Dec 1996;71(12):1182-91. [View Abstract]
  20. Conrotto D, Carbone M, Carrozzo M, et al. Ciclosporin vs. clobetasol in the topical management of atrophic and erosive oral lichen planus: a double-blind, randomized controlled trial. Br J Dermatol. Jan 2006;154(1):139-45. [View Abstract]
  21. Gonzalez-Moles MA, Scully C, Gil-Montoya JA. Oral lichen planus: controversies surrounding malignant transformation. Oral Dis. Apr 2008;14(3):229-43. [View Abstract]

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

Lichen planus on the flexor part of the wrist.

Close-up view of lichen planus.

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

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

Lichen planus on the flexor part of the wrist.

Close-up view of lichen planus.

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

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