**12. Prognosis and outcome**

Protracted involvement is typical for OLP, averaging on 8 years, and ranging up to 20 years. In many cases, OLP inexplicably "burns out" allowing for the cessation of any therapeutic interventions. However, some patients may suffer from the cycle of chronic inflammation followed by healing with scarring, with resultant microstomia, if the bucco-labial mucosa is involved, or loss of buccal sulcal depth, making the provision of oral hygiene by the use of a toothbrush difficult for the patient. In such cases, elective removal of the more posteriorly placed teeth, especially unopposed, non-functional, molar teeth may merit consideration. Plastic surgery interventions to relieve the microstomia are indicated, but are painful and can be of limited benefit (Figure 10).

**Figure 10.** Microstomia secondary to long-standing OLP

#### **12.1. Malignant transformation**

molecules or proteinases) that are induced or regulated by TNF. It was the first TNF antagonist approved for treatment of psoriasis and psoriatic arthritis and is administered as subcutaneous injection. Yarom published a case report in 2007 of a 56-year-old woman with resistant to treatment to the usual immune-suppressant drugs and whose diabetes and hypertension precluded the use of high dose corticosteroids. [64] Subcutaneous etanercept (25 mg twice weekly) was administered with a 90% symptomatic improvement lesions documented 4 week after beginning therapy. After 10 weeks, the patients stopped the treatment because of the expense, which highlights another concern with the use of the new biologic therapies, their

**Alefacept (Amevive):** a recombinant protein that, binds to CD2 on the T cell membrane thereby

cells by interfering and inducing apoptosis of memory-effector T lymphocytes. It is composed of an LFA-3 protein and human IgG1 fragment crystallizable (Fc) domain. [65] The rationale

alefacept induces T-cells apoptosis through natural-killer cells release of granzyme with a

of generalized lichen planus, with OLP, treated with alefacept, with both patients having full resolution of their lesions and remaining free of lesions and symptoms with completion of the course alefacept therapy, suggesting that it may have a disease modifying effect, negating the need for ongoing therapy for patients with seemingly recalcitrant lichen planus, including

**Rituximab:** was approved for the treatment of malignancy by the US Food and Drug Admin‐ istration in 1997, has been used in certain B-cell lymphomas and treatment resistant rheuma‐ toid arthritis. It is a chimeric murine–human monoclonal antibody to CD20 that depletes normal as well as malignant B cells. Currently, rituximab has been introduced into therapies of numerous immune-mediated conditions in dermatology. [67] Parmentier et al reported in 2008, successful treatment with rituximab for muco-cutaneous LP with oesophageal involve‐ ment. [24] There has been no follow-up cases reported since. It is controversial that rituximab targeting B cells could improve T-cell mediated OLP, but it suggests that the humoral arm of

Protracted involvement is typical for OLP, averaging on 8 years, and ranging up to 20 years. In many cases, OLP inexplicably "burns out" allowing for the cessation of any therapeutic interventions. However, some patients may suffer from the cycle of chronic inflammation followed by healing with scarring, with resultant microstomia, if the bucco-labial mucosa is involved, or loss of buccal sulcal depth, making the provision of oral hygiene by the use of a toothbrush difficult for the patient. In such cases, elective removal of the more posteriorly placed teeth, especially unopposed, non-functional, molar teeth may merit consideration. Plastic surgery interventions to relieve the microstomia are indicated, but are painful and can

T-cell lymphocyte numbers. Fivenson et al in 2006, reported two cases

and CD8+

T-cells and

T

blocking the costimulatory molecule LFA-3/CD2, inhibiting the activation of CD4+

for alefacept use in the treatment of lichen planus is the established role for CD4+

the immune system may have some role in the immune-pathogenesis of OLP.

cost.

reduction in the CD4+

168 Skin Biopsy - Diagnosis and Treatment

**12. Prognosis and outcome**

be of limited benefit (Figure 10).

OLP. [66]

The potential for OLP to undergo malignant transformation is controversial. If there is a risk, the risk is very difficult to quantify and possibly so low that it is very difficult to determine if OLP is truly associated with a significant risk for malignant transformation. Prudence would dictate to treat OLP as a potentially malignant lesion. [1, 33] If this approach is favoured, then ongoing, and at the least, annual monitoring, of the oral mucosa, by a clinician experienced in the management of OLP, is indicated. Any lesion suspected to harbour dysplasia and/or frank malignancy (oral squamous cell carcinoma) merits biopsy, and histopathological assessment, preferably by a pathologist experienced in oral pathology. Clinical suspicion should be aroused in the case of a lesion (or lesions) not typical for OLP, a lesion that is heterogeneous in texture and colour (a mixture of erythema and keratosis), or, any isolated area of mucosa that appears to be distinctly unresponsive to therapeutic interventions - such as persistent ulceration - despite clinical improvement in the remainder of the mucosa affected by the OLP. Before undertaking a biopsy, consideration should be given to a trial of topical (and if indicated systemic) corticosteroids and anti-fungal treatments to lessen any associated inflammatory or infectious changes that on histopathological assessment may mask the degree of dysplasia or malignancy within the lesion. [33, 34]

## **13. Conclusion**

Oral lichen planus is a disease that results from CD8+ T cell-mediated apoptosis of basal keratinocytes in response to an unknown endogenous or at times a known exogenous antigen. The resultant raised white lesions tend to develop in sites of trauma (Koebner phenomenon) and may exhibit the presence of slender white lines (Wickham's striae) radiating from the lesions that are generally asymptomatic, observed often by chance and do not warrant ongoing treatment. However, the predominantly erythematous forms of OLP that is the atrophic, ulcerative (erosive) and desquamative gingivitis presentations of OLP can be significantly symptomatic and warrant treatment. A biopsy is prudent, particularly when the disease does not present with its typical manifestations, or when dysplasia or malignancy needs to be excluded. Signs of "liquefaction degeneration" in the basal cell layer, presence of a well-defined band-like zone of cellular infiltration confined to the superficial part of the connective tissue consisting mainly of T-lymphocytes and normal epithelial maturation pattern are hallmarks of OLP. Patch testing may be employed by a specialist with sufficient expertise in the area to differentiate between idiopathic OLP and oral lichenoid contact lesions OLCL if for instance amalgam is suspected as an allergen.

**References**

[1] Al-Hashimi I, Schifter M, Lockhart PB, Wray D, Brennan M, Migliorati CA, et al. Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations.

Oral Lichen Planus

171

http://dx.doi.org/10.5772/56482

[2] Andreasen JO. Oral lichen planus. 1. A clinical evaluation of 115 cases. Oral Surg Or‐

[3] Eisenberg, E. Clinicopathologic patterns of oral lichenoid lesions. Oral Maxillofac

[7] Wickham, LF. Sur un signe pathognomonique delichen du Wilson (lichen plan) stries

[8] Hallopeau H. Sur un cas de lichen de Wilson gingival avec neoplasia voisine dans la

[9] Bouquot JE, Gundlach KK. Oral exophytic lesions in 23,616 white Americans over 35

[10] McCartan BE, Healy CM. The reported prevalence of oral lichen planus: a review

[11] Axe´ll T, Rundquist L. Oral lichen planus – a demographic study. Community Dent

[12] Sugerman PB, Savage NW, Walsh LJ, et al. The pathogenesis of oral lichen planus.

[13] Lodi G, Scully C, Carrozzo M, Griffiths M, Sugerman PB, Thongprasom K. Current controversies in oral lichen planus; report of an international consensus meeting-Part 1. Viral infections and aetiopathopathogenesis. Oral Surg Oral Med Oral Pathol Oral

[14] Sugerman PB, Satterwhite K, Bigby M. Autocytotoxic T-cell clones in lichen planus.

[16] Khan A, Farah CS, Savage NW, et al. Th1 cytokines in oral lichen planus. J Oral Path‐

[17] Wajant H. The Fas signaling pathway: more than a paradigm. Science 2002; 296

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:S25:1-12.

al Med Oral Pathol; 1968; 25: 31–42.

Surg Clin North Am, 1994, 6, 445.

[4] Staubach P. Lichen planus. CME Dermatol 2009; 4: 68-79.

[5] Wilson, E. On lichen planus. J Cutan Med Dis Skin 1869; 3: 117-132.

et punctuations grisatres. Ann Dermatol Syph 1895; 6: 17-20.

région maxillaire. Bull Soc Fr Dermatol Syphiligr 1910;17:32.

years of age. Oral Surg Oral Med Oral Pathol 1986: 62: 284–291.

and critique. J Oral Pathol Med 2008; 37:447–53.

[15] http://www.dako.com/au/ar38/p104620/prod\_products.htm

Oral Epidemiol 1987; 15: 52–6.

Radiol Endod 2005;100:40-51.

Br J Dermatol 2000;142:449-56.

ol Med 2003;32:77-83.

(5573): 1635–6

Crit Rev Oral Biol Med. 2002; 13: 350-65.

[6] Miller RAW. The Koebner phenomenon. Int J Dermatol 1982;21:192-7.

Therapy, for symptomatic patients, initially should focus on patient education on the elimi‐ nation of precipitating or provoking factors. Pharmacotherapies are largely empirical and initially potent topical corticosteroids (betamethasone in Orobase, clobetasone in Orobase, or dexamethasone as a mouthwash suspension) are trialled. Topical calcineurin inhibitors are effective but inferior to topical corticosteroids. Low-dose systemic corticosteroids are useful. Hydroxychloroquine, azathioprine, methotrexate, and mycophenolate may be effective in refractory disease. The efficacy (as well as their long-term safety) of biologic agents remains to better evaluated by larger, prospective studies.

OLP inexplicably burns out after a mean period of 8 years. The risk of malignancy is contro‐ versial but regular surveillance is advisable with biopsies of suspicious areas recommended to detect early dysplastic changes.
