Skip to main content
eScholarship
Open Access Publications from the University of California

Oral lichen planus

  • Author(s): Johnson, Hillary
  • Soldano, Anthony C
  • Kovich, Olympia
  • Long, Wendy
  • et al.
Main Content

Oral lichen planus
Hillary Johnson MD PhD, Anthony C Soldano MD, Olympia Kovich MD, Wendy Long MD
Dermatology Online Journal 14 (5): 20

Department of Dermatology, New York University

Abstract

A 42-year-old woman presented with a 2-year history of persistent, gray-white lip discoloration and discomfort that had not improved after empiric treatment with topical 5-fluorouracil cream. Histopathologic examination demonstrated interface dermatitis with epidermal atrophy. A diagnosis of oral lichen planus was made based on clinicopathologic correlation and treatment with topical tacrolimus ointment was initiated.



Clinical synopsis

A 42-year-old woman presented to the Charles C. Harris Skin and Cancer Pavilion in February, 2007, with a two-year history of persistent lip dryness, peeling, and discoloration that caused discomfort and cosmetic concern. The patient reported that the lesions previously had been diagnosed by outside dermatologists as actinic cheilitis. She had been previously treated with a 5-week course of topical 5-fluorouracil 5 percent cream that induced redness, desquamation, and pain but did not improve the underlying disorder. For the past several months, Aquaphor ointment had been applied to the lips several times a day. There were no lesions in other locations.

The patient denied other medical or dental problems and was otherwise healthy without any systemic complaints. Her only medication was zolpidem as needed for insomnia. There was no family history of any skin or dental disorders. Although the patient had lived in Hawaii for 8 years, she did not experience blistering sunburns and had no history of skin cancer. The patient denied tobacco abuse. Dental history was unremarkable without past dental implantation or restoration.

A shave biopsy was performed. To date, treatment with topical tacrolimus 0.1 percent ointment has not resulted in change in the lesions or provided symptomatic relief.


Physical Examination

A reticular network of slightly-raised, gray-white, fine lines interspersed with diminutive <1-mm, gray-white papules was present on the lower labial surface. On the lower lip was a solitary 1 x 1 mm, erythematous, superficial erosion. The tongue, gingivae, buccal mucosae, and nails appeared normal. Total body cutaneous examination was otherwise unremarkable without suspicious lesions or signs of dermatoheliosis.


Figure 1Figure 2

Histopathology

A complete blood count, comprehensive metabolic panel, hepatic function panel, and thyroid function panel were normal. Hepatitis B virus, hepatitis C virus, anti-nuclear antibody, and rheumatoid factor were negative.


Comment

Oral lichen planus (OLP) is a chronic inflammatory dermatosis of unknown etiology that often involves the mucous membranes. A growing body of evidence supports an immunopathologic mechanism that involves dysregulation of cellular immunity. Immunohistopathologic studies have shown increased numbers of T-cells, macrophages, and mast cells in lesions. Activated CD8+ T-cells were detected within the epithelium adjacent to damaged basal keratinocytes, and ex vivo CD8+ T-cell clones have been shown to induce the apoptosis of autologous keratinocytes and produce immunoregulatory molecules. Clonal, activated, noncytotoxic CD4+ T-cells have been localized in lesions along with increased numbers of Langerhans cells with upregulated expression of MHC class II. Lesional keratinocytes also expressed MHC class II molecules. Several cytokines, chemokines, and proteinases have been detected in both in-situ and in-vitro studies. Taken together, these data have led to the hypothesis that the presentation of an altered antigen may trigger basal keratinocyte apoptosis by cytotoxic CD8+ T-cells in a chronic process that is fueled by soluble inflammatory mediators [1]. Postulated initiating events that may trigger OLP include infection, trauma, systemic medication, and contact sensitivity; however, evidence proving a causal relationship is lacking [1-5].

Oral lichen planus has a prevalence rate reported between 0.1 percent and 4 percent. It most commonly affects patients of ages 30 to 60 years and is found more frequently in women. While OLP is frequently observed in patients with cutaneous lichen planus, it may be the only finding in approximately 25 percent. The reticulate clinical presentation displaying the characteristic Wickham's striae is most common; however, numerous clinical forms may be observed in isolation or in combination (e.g. atrophic, erosive, bullous, popular, pigmented, and plaque-like). Diagnosis may be made using clinical features alone or may require clinicopathologic correlation for atypical presentations or to rule out malignant conditions [6-9].

Differential diagnosis includes oral lichenoid reactions and other white or gray-colored oral lesions [10]. Oral lichenoid contact lesions most commonly result from dental amalgams used in restorative procedures [11]. Oral lichenoid drug reactions can be caused by hypoglycemic agents, nonsteroidal anti-inflammatory agents, and, less frequently, penicillamine or gold salts. Allogeneic bone-marrow or stem-cell transplant patients can develop oral lichenoid lesions of graft-versus-host-disease. The clinical context can help distinguish these conditions as well as oral disorders due to nutritional deficiencies, autoimmune bullous disorders, and discoid lupus erythematosus. Actinic cheilitis typically occurs in older patients and is accompanied by additional manifestations of dermatoheliosis [10, 13]. Histopathologic features include basal keratinocyte apotosis and a lichenoid interface lymphocytic reaction. This pattern also can appear in other oral lichenoid reactions, erythema multiforme, discoid lupus erythematosus, and graft-versus-host-disease [10, 12, 13].

Annual monitoring via clinical examination and/or histopathologic analysis is recommended for potential malignant transformation, which can occur with chronic inflammation [14-19]. Development of oral squamous-cell carcinoma in OLP has been reported at a rate of 0.2 percent to 0.5 percent and occurs more often in the erosive or bullous forms. Novel techniques that may be developed for future detection of dysplasia or malignant conditions include the use of molecular markers or brush sampling for cytopathologic assessment. Additionally, patients should avoid possible mutagens such as tobacco and alcohol [20-22]. Routine screening for hepatitis C virus (HCV) is controversial. OLP and HCV have been frequently associated in anectdotal reports, particularly in Mediterranean and Japanese populations. However, a causative role for HCV has not been demonstrated in prospective studies. Testing for HCV in a patient with OLP would be considered reasonable [23, 24].

Management of non-ulcerative OLP typically involves medical modalities, which include topical or intralesional glucocorticoids, topical calcineurin inhibitors, topical or oral retinoids, and phototherapy [10, 25]. Asymptomatic, reticulate OLP may be clinically monitored without medical therapy. Placebo-controlled trials have demonstrated effectiveness of both topical glucocorticoids and topical calcineurin inhibitors; however, there is a tendency for recurrence once therapy is discontinued [25, 28]. Routine use of topical glucocorticoids frequently has been associated with the development of oral candidiasis [29]. Efficacy of topical and systemic retinoids has been demonstrated to be inferior to topical glucocorticoids, with the reticular OLP subtype responding the best [30]. Topical tacrolimus ointment has been shown to be effective in small prospective studies with local irritation as the most common side effect. In contrast to topical glucocorticoids, topical tacrolimus ointment lacks an association with oral candidiasis [28]. A recent anectodotal report of the development of squamous carcinoma of the tongue in a patient with OLP using topical tacrolimus ointment has raised questions of its use with regard to the FDA's Black Box warning of a theoretical increased risk of malignant conditions [31]. PUVA photochemotherapy has been helpful for severe OLP but has many undesirable side effects in addition to its oncogenic potential. Efalizumab, methylene-blue-mediated photodynamic therapy, and excimer laser treatment have been noted to successfully treat individual cases of recalcitrant OLP [32-35].

References

1. Lodi G, et al. Current controversies in oral lichen planus: report of an international consensus meeting. Part 1. Viral infections and etiopathogenesis. OOOOE 2005; 100:40

2. Ichimura M, et al. Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus. J Oral Pathol Med 2006; 35:167

3. Carrozzo M, et al. Tumor necrosis factor-alpha and interferon-gamma polymorphisms contribute to susceptibility to oral lichen planus. J Invest Dermatol 2004; 122:87

4. Yamamato T, et al. Characteristic cytokines generated by keratinocytes and mononuclear infiltrates in oral lichen planus. J Invest Dermatol 1995; 104:784

5. Mazzarella N, et al. Matrix metalloproteinase gene expression in oral lichen planus: erosive vs. reticular forms. J Eur Acad Dermatol Venereol 2006; 20:953

6. Eisen D, et al. Oral lichen planus: clinical features and management. Oral Dis 2005; 11:338

7. Silverman S, et al. A prospective follow-up study of 570 patients with oral lichen planus: persistence, remission, and malignant association. OOOOE 1985; 60:30

8. Xue J-L, et al. A clinical study of 674 patients with oral lichen planus in China. J Oral Pathol Med 2005; 34:467

9. Ingafou M, et al. Oral lichen planus: a retrospective study of 690 British patients. Oral Dis 2006; 12:463

10. Al-Hashimi I, et al. Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations. OOOOE 2007; article in press

11. Laeijendecker R, et al. Oral lichen planus and allergy to dental amalgam restorations. Arch Dermatol 2004; 140:1434

12. Thornhill M, et al. The role of histopathological characteristics in distinguishing amalgam-associated oral lichenoid reactions and oral lichen planus. J Oral Pathol Med 2006; 35:233

13. Juneja M, et al. Histochemical analysis of pathological alterations in oral lichen planus and oral lichenoid lesions. J Oral Sci 2006; 4:185

14. Lodi G, et al. Current controversies in oral lichen planus: report of an international consensus meeting. Part 2. Clinical management and malignant transformation. Oral Surg Oral Med Oral Pathol 2005; 100:164

15. Van der Meij EH, et al. The possible premalignant character of oral lichen planus and oral lichenoid lesions: a prospective five-year follow-up study of 192 patients. Oral Onc 2007; article in press

16. Laeijendecker R, et al. Premalignant nature of oral lichen planus. Acta Derm Venereol 2005; 85:516

17. Mignogna M, et al. Immune activation and chronic inflammation as the cause of malignancy in oral lichen planus: is there any evidence? Oral Oncol 2004; 40:120

18. Bascones C, et al. Apoptosis and cell cycle arrest in oral lichen planus: hypothesis on their possible influence on its malignant transformation. Arch Oral Biol 2005; 50:873

19. Montebugnoli L, et al. High proliferative activity and chromosomal instability in oral lichen planus. Int J Oral Maxillofac Surg 2006; 35:1140

20. Maraki D, et al. Cytologic and DNA-cytometric examination of oral lesions in lichen planus. J Oral Pathol Med 2006; 35:227

21. Mattila R, et al. Immunohistochemical study on topoisomerase II alpha, Ki-67 and cytokeratin-19 in oral lichen planus lesions. Arch Derm Res 2007; 298:381

22. Buajeeb W, et al. Frequency of micronucleated exfoliated cells in oral lichen planus. Mut Res 2007; 627:191

23. Lodi G, et al. Lichen planus and hepatitis C virus: a multicentre study of patients with oral lesions and a systematic review. Br J Dermatol 2004; 151:1172

24. Laeijendecker R, et al. Oral lichen planus and hepatitis C virus infection. Arch Dermatol 2005; 141:906

25. Zakrzewska JM, et al. A systematic review of placebo-controlled randomized clinical trials of treatments used in oral lichen planus. Br J Dermatol 2005; 153:336

26. Xia J, et al. Short-term clinical evaluation of intralesional triamcinolone acetonide injection for ulcerative oral lichen planus. J Oral Pathol Med 2006; 35:327

27. Thongprasom K, et al. Expression of TNF-alpha in oral lichen planus treated with fluocinolone acetonide 0.1%. J Oral Pathol Med 2006; 35:161

28. Byrd J, et al. Response of oral lichen planus to topical tacrolimus in 37 patients. Arch Dermatol 2004; 140:1508

29. Jainkittivong A, et al. Candida in oral lichen planus patients undergoing topical steroid therapy. OOOOE 2007; article in press

30. Buajeeb W, et al. Efficacy of topical retinoic acid compared with topical fluocinolone acetonide in the treatment of oral lichen planus. OOOOE 2000; 83:21

31. Becker JC, et al. The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report. BMC Cancer 2006; 6:7

32. Cheng A, Mann C. Oral erosive lichen planus treated with efalizumab. Arch Dermatol 2006; 142:680

33. Trehan M, Taylor C. Low-dose excimer 308-nm laser for the treatment of oral lichen planus. Arch Dermatol 2004; 140:415

34. Aghahosseini F, et al. Methylene blue-mediated photodynamic therapy: a possible alternative treatment for oral lichen planus. Lasers Surg Med 2006; 38:33

35. Guyot AD, et al. Treatment of refractory erosive oral lichen planus with extracorporeal photochemotherapy: 12 cases. Br J Dermatol 2007; 156:553

© 2008 Dermatology Online Journal