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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 32  |  Issue : 3  |  Page : 284-292

Management of oral Lichen Planus based on the existing clinical practice guidelines


Department of Oral Medicine and Radiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India

Date of Submission06-Apr-2020
Date of Decision18-May-2020
Date of Acceptance01-Jul-2020
Date of Web Publication29-Sep-2020

Correspondence Address:
Dr. T N Uma Maheswari
Department of Oral Medicine and Radiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaomr.jiaomr_55_20

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   Abstract 


Lichen planus is a chronic inflammatory mucocutaneous disorder that affects oral and genital mucous membranes, skin, nails, and scalp. Oral lichen planus (OLP) is the mucosal counterpart of cutaneous Lichen planus. Clinical practice guidelines (CPG) are statements that include recommendations intended to optimize patient care. These guidelines are formulated by using a systematic review of evidence and an assessment of the benefits and harms of alternative care options. Diagnosis and management of patients with OLP continue to challenge even the most experienced clinician. To provide optimum care to the patients a decision tree algorithm needs to be formulated. This article compares the existing clinical practice guidelines available in the literature and a formulated decision tree algorithm.

Keywords: Clinical practice guidelines, decision tree algorithm, diagnostic criteria, management, oral lichen planus


How to cite this article:
Uma Maheswari T N, Chaudhary M. Management of oral Lichen Planus based on the existing clinical practice guidelines. J Indian Acad Oral Med Radiol 2020;32:284-92

How to cite this URL:
Uma Maheswari T N, Chaudhary M. Management of oral Lichen Planus based on the existing clinical practice guidelines. J Indian Acad Oral Med Radiol [serial online] 2020 [cited 2020 Nov 1];32:284-92. Available from: https://www.jiaomr.in/text.asp?2020/32/3/284/296587




   Introduction Top


Lichen ruber planus was the initial clinical description of lichen planus coined by Ferdinand Ritter von Hebra in 1860, the clinical description was further refined by Erasmus Wilson and coined the term Lichen planus in 1869.[1] Lichen planus is a chronic disease affecting the skin, hair (lichen planopilaris) scalp, nail, and oral mucosa.[2] Unlike cutaneous lichen planus which is self-limiting, a pruritic oral variant of lichen planus is characteristic of relapses and remissions.[3] Both clinical and histological examinations are required for the diagnosis of oral lichen planus but classic reticular lesions can be diagnosed on its characteristic clinical appearances.[4],[5],[6],[7] The differential diagnosis of oral lichen planus includes a wide range of mucosal lesions like lichenoid contact lesions, lichenoid drug reactions, and lichenoid lesions of graft versus host disease. Systemic medications like nonsteroidal anti-inflammatory drugs, antihypertensives, and oral hypoglycemics can contribute to the development of oral lichenoid reactions (OLR).[7],[8] Amalgam, gold, and nickel from dental restorative material may also be related to localizing OLR in some patients.[9] Treatment of symptomatic OLP varies considerably and ranges from the elimination of local triggering factors, local, and systemic interventions and long-term pharmacological therapies.[10] Oral lichen planus is associated with increased risk of malignant transformation which adds even more complexity in the management of oral lichen planus.[11]

There are three existing clinical practice guidelines available in the literature for the management of oral lichen planus. M.D. Mignogna et al. in 2001 on early diagnosis of oral squamous cell carcinoma arising in oral lichen planus based on 5-year experience, The British Society for Oral Medicine—Guidelines for the Management of Oral Lichen Planus in 2010 and American Academy of Oral Medicine (AAOM) Clinical Practice Statement in 2016.[12],[13],[14] The main aim of this article is to create a decision tree algorithm from the preexisting clinical practice guidelines for the management of oral lichen planus.


   Epidemiology of Oral Lichen Planus Top


The prevalence of OLP in the general adult population is 0.5–2%.[7],[15],[16] The male to female sex ratio is 2:1 and the age of onset is between 30 and 60 years.[17],[18],[19] However, there have been case reports of OLP occurring in children.[20]

Etiology

The exact etiology is not known but various predisposing factors involved in the pathogenesis of oral lichen planus are explained in [Table 1] and [Figure 1].
Table 1: Etiology of oral lichen planus

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Figure 1: Etiopathogenesis of oral lichen planus

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Pathophysiology

Cellular-mediated immunity, initiated by predisposing factors results in the production of Tumor Necrosis Factor-alpha (TNF-a), Interferon- cytokine (IFN-c), and keratinocyte, T cell or antigen- presenting cell associations.[21],[22],[23] The increased production of T-helper 1 (Th1) cytokines occurs in the early event in OLP, genetic polymorphism of cytokines and IFN-gamma will lead to the development of oral mucosal lesions, increase in the frequency of 308A TNF-alpha allele will lead to the development of skin lesions. A hypothesis of the pathogenesis of OLP was introduced by Sugerman et al. and is based on a theoretical interaction between CD8+ T cells and CD4+ T cells through a “request cytotoxic activity” (RCA) cell surface molecule.[24] The activated CD8+ T cells can trigger keratinocytes apoptosis through TNF-alpha or a Fas–Fas Ligand mechanism.[25] The role of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are proven to initiate pro-inflammatory cytokines which will lead to inflammation.[26]

RANTES (regulated on activation, normal T cell expressed and secreted) a chemokine family also plays a role in pathogenesis by activating the number of cells like lymphocytes, monocytes, natural killer cells, eosinophils, basophils, and mast cells in oral lichen planus and the cell surface receptors are also increased.[27]


   Clinical Features Top


The clinical subtypes of oral lichen planus are reticular, plaque-like, atrophic, erosive/ulcerative, popular, and bullous forms. The clinical features are explained in [Table 2]. The most common of these is the reticular, erosive/ulcerative, and plaque-like subtypes.[28],[29] Bullous and papular forms are rare in the oral mucosa.[30] The World Health Organization (WHO) devised a set of clinicopathological criteria in 1978 which was revised in 2003 [Table 3].
Table 2: Clinical features of oral lichen planus[27],[28],[29]

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Table 3: Modified WHO diagnostic criteria - 2003

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The reported rate of OLP malignant transformation varied between 0 and 10%.[31] A recent meta-analysis reported that 1.1% of OLP lesions progress into OSCC with a higher incidence in smokers, alcohol users, and those infected with the hepatitis C virus.[32] It seems that erosive OLP is the type that has the highest frequency to progress into OSCC.[12],[33] Most commonly, malignant transformation occurs in lesions that are localized on the tongue.[34] Muñoz et al. have found that, on average, it takes 5.5 years for OLP lesions to transform into an established OSCC.

Clinicians can improve patients' survival rates if a cancerous lesion is detected at an early stage, or if a precursor lesion (dysplasia) is discovered and treated before malignant progression.[35]

Histopathology

Histopathological features include liquefactive degeneration of the basal cells, colloid bodies (Civatte, hyaline, cytoid), homogeneous infiltrate of lymphocytes and histiocytes in a dense, band-like pattern along with the epithelium-connective tissue interface in the superficial dermis, cytologically normal maturation of the epithelium, saw-tooth rete ridges, and hyperkeratosis (orthokeratosis or parakeratosis).[36] Discontinuity in the epithelium can be seen in erosive or ulcerative forms.

Investigations

Incisional biopsy with the histopathological study is done to confirm the clinical diagnosis and for evaluating the status of epithelial dysplasia and malignancy.[37] Gingival lichen planus requires direct immunofluorescence, it shows a linear pattern and intense positive fluorescence with anti-fibrinogen outlining the basement membrane zone and cytoid-like bodies with positive immunoglobulin M labeling.[37]

Recent clinical diagnostic tools for early detection of oral cancer include tolonium chloride or toluidine blue dye, Oral CDx brush biopsy kits, salivary diagnostics, and lastly optical imaging systems. Depending on the type of light, and the imaging approaches used, optical imaging of the oral tissues can detect minimal changes within the tissues, such as alterations in tissue architecture and composition; expression of specific biomarkers, vascularity/angiogenesis and perfusion; microanatomy and tissue boundary integrity (e.g., potential invasiveness of lesions).[38],[39]

The most common ones that have been marketed to dentists include ViziLite (Zila, Batesville, AR, USA), VELscope (LED Dental Inc., Vancouver, Canada), DIFOTI (Electro-Optical Sciences, Inc., Irvington, NY, USA) and Identafi 3000 (DentalEZ, Bay Minette, AL, USA). All these methods have their advantages and disadvantages but unfortunately, these non-invasive tools have failed in their practical implication in the community set up, as patients are still being diagnosed in advanced stages of oral cancer.[40],[41]


   Management Based on Clinical Practice Guidelines Top


These management guidelines were given by The British Society for Oral Medicine—Guidelines for the Management of Oral Lichen planus explained in [Table 4]
Table 4: British society of oral medicine- clinical practice guidelines for management of oral lichen planus

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The American Academy of Oral Medicine (AAOM)

  1. Patients with a diagnosis of OLP or OLL should be periodically monitored by an experienced clinician for possible malignant and premalignant lesions and these suspicious areas biopsied
  2. At the time of diagnosis of OLP and OLL, patients should be counseled about the low but potential increased risk of oral cancer so that they understand that periodic examinations are necessary even if the patients are asymptomatic or their symptoms are well controlled
  3. The AAOM strongly supports the development of well-planned, multicentered, prospective studies of malignancy and OLP to further determine the risk of oral cancer developing in patients with OLP and OLL and subsets of these patients with the greatest risk of oral malignancy.


A 980-nm diode laser,[42] CO2 laser evaporation,[43] biostimulation with a pulsed diode laser using 904-nm pulsed infrared rays[44] and low-dose excimer 308-nm laser with UV-B rays and photodynamic therapy (PDT) have been tried.[45] All types of laser destroy the superficial epithelium containing the target keratinocytes by protein denaturation. A deeper penetrating beam like the diode laser destroys the underlying connective tissue with the inflammatory component along the epithelium.

CPG based on a five-year clinical trial by M.D. Mignogna[12]et al.

  • For the prevention of malignant transformation a minimum of 4 months follow up and a maximum of 12 months follow up is required
  • With five years of follow up 4.9% of patients had malignant transformation
  • In patients with tobacco usage, the malignant transformation was 3.7%.


The recent clinical trials for Oral Lichen Planus have been explained in[Table 5].
Table 5: Recent clinical trails for oral lichen planus

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Clinical trial by Qataya PO[46]et al.

  • Two Selenium forms (novel topical hydrogel and systemic oral capsules) for treating erosive OLP based on clinical evaluation and salivary oxidative stress markers
  • Treatment lasted for 6 weeks; patients were clinically evaluated at baseline, 6, and 12 weeks. Biochemical analysis for salivary malondialdehyde (MDA) and total antioxidant capacity (TAC) levels at baseline and 6 weeks was performed
  • Significant reduction in signs and symptoms in response to all treatment modalities. No significant difference between the two groups at 6 weeks. At 12 weeks, topical selenium had significantly lower pain scores. Salivary MDA levels showed a significant decrease in patients of systemic selenium. TAC levels showed no significant difference in response to treatment
  • Selenium: A sole treatment for erosive oral lichen planus (randomized-controlled clinical trial). Selenium can be proposed as a treatment for OLP.


Clinical trial by Yeshurun et al.[47]

  • Twenty-one patients with erosive, biopsy-confirmed oral LP. They were prescribed hydroxychloroquine sulphate 400 mg/day
  • Symptomatic improvement was evaluated using a visual analog scale into three groups: No change, moderate to marked improvement and complete remission. Response to therapy was observed after 2-4 months
  • Five (24%) patients obtained complete remission, 12 (57%) patients showed moderate to marked improvement, 3 (14%) patients did not improve at all and in one patient therapy was terminated after 1 month due to side effects.
  • The trial concluded that Hydroxychloroquine sulphate may be an effective and relatively safe treatment for erosive oral LP.


Clinical trial by Patel et al.[48]

  • For the treatment of lichen planus tropicus or lichen planus interventions 1 and 2 were given. Intervention 1 included for controls the standard treatment of oral prednisolone 0.5 mg per kg daily until complete recovery or up to 8 weeks Intervention 2 included enoxaparin 5 mg subcutaneously weekly was given until complete remission or a maximum of 8 weeks
  • Primary outcome was the extension of active lesions. Timepoint: Before treatment-weekly in treatment period- in 1, 3, and 6 months following end of treatment. Method of measurement: Percentage of the skin surface. Pruritus. Timepoint: Before treatment-weekly in treatment period- in 1, 3, and 6 months following the end of treatment. Method of measurement: Visual analog scale (VAS)
  • Secondary outcome was Bleeding. Timepoint: Weekly in the period of treatment. Method of measurement: Observation (yes or no). Hypersensitivity. Timepoint: Weekly in the period of treatment. Method of measurement: Observation (yes or no).


Clinical trial by Zakaria et al.[49]

  • Forty-two patients presenting clinically with atrophic OLP were involved in the study
  • They were randomly divided into three equivalent groups to be managed with topical corticosteroid gel as a control group, topical pomegranate seed extract gel as Group S, and topical pomegranate peel extract gel as Group P
  • Assessment of pain, sign scores and oral health impact profile- 14 (OHIP- 14) were carried out in each group before and after the user management protocols. The results showed a significant decrease in sign; pain scores and OHIP-14 values which were recorded in group S and group P
  • Concluded that this contemplates using topical pomegranate seeds and peel extracts gel offers a new promising natural, safe, and effective management of OLP.


The other natural alternative used a buccal tablet containing 300 mg of green tea extract which adheres to the buccal mucosa slowly releasing the polyphenols along around 8 hours 2 times a day for four weeks.

Clinical trial by Tim A. Hodgson et al.[50]

  • The long-term safety and clinical benefit of topical tacrolimus for the management of erosive or ulcerative oral lichen planus have not been evaluated
  • 50adults (39 female 11 male; group median age 59, range 29–88 years) with symptomatic, erosive, or ulcerative lichen planus. 0.1% topical tacrolimus ointment was applied twice daily to symptomatic mucosal lesions
  • Topical tacrolimus was applied for a median time of 19.8months (range 2–39months) in this patient group. Fourteen percent of the patients had complete resolution of ulcers or erosions, 80% partial resolution and 6% reported no clinical benefit
  • The most common adverse effects were a burning sensation (16%) at the site of application and transient taste disturbance (8%). No significant, long-standing changes in hepatic or renal biochemistry were observed
  • The mean tacrolimus level decreased with the duration of therapy from 2.7μg\l (week 1) to 0.5μg\l (week 32). 0.1% topical tacrolimus is an effective means of controlling the symptoms and signs of erosive or ulcerative oral lichen planus and has no notable adverse effects over a mean duration of application of 19.8 months.


Clinical trial by Siponen M et al.[51]

  • Twenty-seven patients with symptomatic OLP were randomly allocated to receive 0.1% tacrolimusointment (n = 11), 0.1% triamcinolone acetonide paste (n = 7) or Orabase paste (n = 9), applied on the oral mucosa 3 times a day for 3 weeks
  • If the clinical score (CS) dropped a minimum of 20% (interpreted as a response), the patients continued the same medication for another 3 weeks
  • If the CS dropped less than 20% or increased (non-response), the patients were switched to 0.1%tacrolimusfor 6 weeks
  • The primary outcome measure was the change in the CS from baseline to week 3. The participants were blinded to the intervention during the first 6 to 9 weeks and the investigator for the first 3-6 weeks
  • At week 3, tacrolimus and triamcinolone groups responded to treatment more often than the placebo group (63.6% and 57.1%, respectively vs. 11%, P = 0.004). Three cases that did not initially respond to triamcinolone, and were switched to tacrolimus, showed a decrease in CS at weeks 6 and 9.


Based on all clinical trials, a new decision tree analysis is proposed [Figure 2]. Oral Lichen planus is classified into three types: Reticular, Erosive, and Recalcitrant.
Figure 2: Decision tree analysis

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  • Reticular lichen planus can be further classified as symptomatic and asymptomatic. For asymptomatic, no treatment is required, only a periodic follow up is done whereas for symptomatic reticular lichen planus topical anesthetic agents like benzydamine hydrochloride (0.15%) mouthwash is used. The biopsy is must to confirm the diagnosis of erosive lichen planus. The clinical symptoms can be mild or severe. In case of mild symptoms, systemic tablet selenium 200mcg,[52] tablet hydroxychloroquine sulphate 400 mg/day or tablet oral prednisolone 0.5 mg per kg can be prescribed. For topical corticosteroids, the dosage and duration are given as per the patient's need. In case of severe ulcerations systemic corticosteroids-tablet prednisone 30 to 60 mg daily for three to six weeks is given, then the dose is tapered over the next four to six weeks. If the severe ulceration is accompanied by the candidal infection then antifungal therapy can be given. For recalcitrant oral lichen planus, topical tacrolimus, 1% topical cream of pimecrolimus or topical cyclosporines with 5 ml of solution (500 mg) of cyclosporine in the mouth three times a day for three months can be prescribed.[52]


Differences between Oral Lichen Planus and Oral Lichenoid Lesions (OLL) with clinical figures of lesions is shown in [Figure 3] and [Table 6].[53]
Figure 3: a:Oral lichen planus b:oral lichenoid reactions

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Table 6: Clinical differences between oral lichen planus and oral lichenoid reactions

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Management protocol for Oral Lichenoid Lesion (OLL) is the use of topical corticosteroids for symptomatic relief. It is considered to be the first line of treatment. It is safe to use, low cost and can be used in almost all the patients. The second line of treatment is the removal of causative agents. It can be combined with the use of topical corticosteroids. Oral prophylaxis, regular use of mouthwashes, and regular polishing of restorations are other treatment methods for OLL.[53]


   Conclusion Top


Proper clinical and histopathological examination of Oral lichen planus will lead to a definitive diagnosis. Treatment of oral lichen planus should be personalized. A generalized treatment protocol is not possible. Obtaining recent clinical trials is essential for effective treatment of oral lichen planus. Timely diagnosis and management will help in the prevention of oral squamous cell carcinoma development.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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